{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T20:07:14Z","timestamp":1779307634762,"version":"3.51.4"},"reference-count":101,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004442","name":"Narodowym Centrum Nauki","doi-asserted-by":"publisher","award":["2023\/49\/B\/NZ5\/03438"],"award-info":[{"award-number":["2023\/49\/B\/NZ5\/03438"]}],"id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"publisher"}]},{"name":"2024 L\u2019Oreal-UNESCO for Women in Science program in Poland"},{"name":"Engles Family Fund for Research in TSC and LAM"},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["CC2037"],"award-info":[{"award-number":["CC2037"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["CC2037"],"award-info":[{"award-number":["CC2037"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["CC2037"],"award-info":[{"award-number":["CC2037"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/Y008138\/1"],"award-info":[{"award-number":["MR\/Y008138\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"TSC Alliance Biosample Seed Grant"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Neuropathol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Tuberous sclerosis complex (TSC) is a rare disease caused by mutations in\n                    <jats:italic>TSC1<\/jats:italic>\n                    and\n                    <jats:italic>TSC2,<\/jats:italic>\n                    resulting in activation of mechanistic target of rapamycin complex 1 (mTORC1). Neurological manifestations in TSC patients include epilepsy, autism and intellectual disability. Two types of brain lesions, cortical tubers and subependymal giant cell astrocytomas (SEGAs), cause the majority of neurological manifestations in TSC. We have limited understanding of the molecular changes that occur in tubers and SEGAs and how these contribute to disease pathogenesis. To investigate this, we performed proteomic and phosphoproteomic analysis of TSC patient tuber and SEGA tissue. Tubers showed evidence of alterations in mitochondrial respiration, cytoskeleton organisation and neuronal function. However, we were unable to detect mTORC1 activation in tubers, likely due to the small number of cells with complete inactivation of\n                    <jats:italic>TSC1<\/jats:italic>\n                    or\n                    <jats:italic>TSC2<\/jats:italic>\n                    . By contrast, SEGAs showed evidence of strong mTORC1 activation and large-scale changes in the proteome and phosphoproteome. SEGAs exhibited increased expression of ribosomal proteins and activation of a neuroinflammatory response. Phosphoproteomics identified 6060 phosphosites within 2154 proteins increased in SEGAs. Phosphorylation of multiple proteins involved in RNA-metabolism, including mRNA splicing, was increased in SEGAs. Consistent with this, we found evidence of extensive alterations in mRNA transcript splicing in SEGA tissue that is shared with a wide range of cancers. These data greatly expand the repertoire of known mTORC1 target proteins in the human brain and reveal that large-scale mis-regulation of mRNA splicing may promote the formation of SEGAs in TSC.\n                  <\/jats:p>","DOI":"10.1007\/s00401-026-03022-5","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T19:23:54Z","timestamp":1779305034000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The phosphoproteomic landscape of the neurological manifestations in tuberous sclerosis complex"],"prefix":"10.1007","volume":"151","author":[{"given":"Marie","family":"Girodengo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simeon R.","family":"Mihaylov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Klonowska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Mantoan Ritter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen R.","family":"Flynn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Mark","family":"Skehel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elias","family":"Bou Farhat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleonora","family":"Aronica","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"White","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Kwiatkowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sila K.","family":"Ultanir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph M.","family":"Bateman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"3022_CR1","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1111\/j.1468-1331.2009.02567.x","volume":"16","author":"ME Adriaensen","year":"2009","unstructured":"Adriaensen ME, Schaefer-Prokop CM, Stijnen T, Duyndam DA, Zonnenberg BA, Prokop M (2009) Prevalence of subependymal giant cell tumors in patients with tuberous sclerosis and a review of the literature. Eur J Neurol 16:691\u2013696. https:\/\/doi.org\/10.1111\/j.1468-1331.2009.02567.x","journal-title":"Eur J Neurol"},{"key":"3022_CR2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004624","volume":"10","author":"A Avet-Rochex","year":"2014","unstructured":"Avet-Rochex A, Carvajal N, Christoforou CP, Yeung K, Maierbrugger KT, Hobbs C et al (2014) Unkempt is negatively regulated by mTOR and uncouples neuronal differentiation from growth control. PLoS Genet 10:e1004624. https:\/\/doi.org\/10.1371\/journal.pgen.1004624","journal-title":"PLoS Genet"},{"key":"3022_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.102788","author":"P Baskaran","year":"2022","unstructured":"Baskaran P, Mihaylov SR, Vinsland E, Shah K, Granat L, Ultanir SK et al (2022) Phosphorylation of the novel mTOR substrate Unkempt regulates cellular morphogenesis. J Biol Chem. https:\/\/doi.org\/10.1016\/j.jbc.2022.102788","journal-title":"J Biol Chem"},{"key":"3022_CR4","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1016\/j.cmet.2020.08.007","volume":"32","author":"TM Batista","year":"2020","unstructured":"Batista TM, Jayavelu AK, Wewer Albrechtsen NJ, Iovino S, Lebastchi J, Pan H et al (2020) A cell-autonomous signature of dysregulated protein phosphorylation underlies muscle insulin resistance in Type 2 Diabetes. Cell Metab 32:844-859.e845. https:\/\/doi.org\/10.1016\/j.cmet.2020.08.007","journal-title":"Cell Metab"},{"key":"3022_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.04.013","author":"S Battaglioni","year":"2022","unstructured":"Battaglioni S, Benjamin D, W\u00e4lchli M, Maier T, Hall MN (2022) mTOR substrate phosphorylation in growth control. Cell. https:\/\/doi.org\/10.1016\/j.cell.2022.04.013","journal-title":"Cell"},{"key":"3022_CR6","doi-asserted-by":"publisher","first-page":"1814","DOI":"10.1016\/j.cell.2022.04.013","volume":"185","author":"S Battaglioni","year":"2022","unstructured":"Battaglioni S, Benjamin D, W\u00e4lchli M, Maier T, Hall MN (2022) mTOR substrate phosphorylation in growth control. Cell 185:1814\u20131836. https:\/\/doi.org\/10.1016\/j.cell.2022.04.013","journal-title":"Cell"},{"key":"3022_CR7","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.eplepsyres.2007.10.002","volume":"78","author":"K Boer","year":"2008","unstructured":"Boer K, Jansen F, Nellist M, Redeker S, van den Ouweland AM, Spliet WG et al (2008) Inflammatory processes in cortical tubers and subependymal giant cell tumors of tuberous sclerosis complex. Epilepsy Res 78:7\u201321. https:\/\/doi.org\/10.1016\/j.eplepsyres.2007.10.002","journal-title":"Epilepsy Res"},{"key":"3022_CR8","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1093\/jnen\/nlaa040","volume":"79","author":"A Bongaarts","year":"2020","unstructured":"Bongaarts A, de Jong JM, Broekaart DWM, van Scheppingen J, Anink JJ, Mijnsbergen C et al (2020) Dysregulation of the MMP\/TIMP proteolytic system in subependymal giant cell astrocytomas in patients with tuberous sclerosis Complex: modulation of MMP by MicroRNA-320d in vitro. J Neuropathol Exp Neurol 79:777\u2013790. https:\/\/doi.org\/10.1093\/jnen\/nlaa040","journal-title":"J Neuropathol Exp Neurol"},{"key":"3022_CR9","doi-asserted-by":"publisher","first-page":"95516","DOI":"10.18632\/oncotarget.20764","volume":"8","author":"A Bongaarts","year":"2017","unstructured":"Bongaarts A, Giannikou K, Reinten RJ, Anink JJ, Mills JD, Jansen FE et al (2017) Subependymal giant cell astrocytomas in tuberous sclerosis complex have consistent TSC1\/TSC2 biallelic inactivation, and no BRAF mutations. Oncotarget 8:95516\u201395529. https:\/\/doi.org\/10.18632\/oncotarget.20764","journal-title":"Oncotarget"},{"key":"3022_CR10","doi-asserted-by":"publisher","first-page":"2863","DOI":"10.1007\/s10571-021-01157-5","volume":"42","author":"A Bongaarts","year":"2022","unstructured":"Bongaarts A, Mijnsbergen C, Anink JJ, Jansen FE, Spliet WGM, den Dunnen WFA et al (2022) Distinct DNA methylation patterns of subependymal giant cell astrocytomas in tuberous sclerosis complex. Cell Mol Neurobiol 42:2863\u20132892. https:\/\/doi.org\/10.1007\/s10571-021-01157-5","journal-title":"Cell Mol Neurobiol"},{"key":"3022_CR11","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1093\/brain\/awz370","volume":"143","author":"A Bongaarts","year":"2020","unstructured":"Bongaarts A, van Scheppingen J, Korotkov A, Mijnsbergen C, Anink JJ, Jansen FE et al (2020) The coding and non-coding transcriptional landscape of subependymal giant cell astrocytomas. Brain 143:131\u2013149. https:\/\/doi.org\/10.1093\/brain\/awz370","journal-title":"Brain"},{"key":"3022_CR12","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/s41568-022-00541-7","volume":"23","author":"RK Bradley","year":"2023","unstructured":"Bradley RK, Anczuk\u00f3w O (2023) RNA splicing dysregulation and the hallmarks of cancer. Nat Rev Cancer 23:135\u2013155. https:\/\/doi.org\/10.1038\/s41568-022-00541-7","journal-title":"Nat Rev Cancer"},{"key":"3022_CR13","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1093\/jnen\/63.12.1236","volume":"63","author":"JA Chan","year":"2004","unstructured":"Chan JA, Zhang H, Roberts PS, Jozwiak S, Wieslawa G, Lewin-Kowalik J et al (2004) Pathogenesis of tuberous sclerosis subependymal giant cell astrocytomas: biallelic inactivation of TSC1 or TSC2 leads to mTOR activation. J Neuropathol Exp Neurol 63:1236\u20131242","journal-title":"J Neuropathol Exp Neurol"},{"key":"3022_CR14","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1186\/s13023-020-01517-2","volume":"15","author":"WC Chu","year":"2020","unstructured":"Chu WC, Chiang LL, Chan DC, Wong WH, Chan GC (2020) Prevalence, mortality and healthcare economic burden of tuberous sclerosis in Hong Kong: a population-based retrospective cohort study (1995-2018). Orphanet J Rare Dis 15:264. https:\/\/doi.org\/10.1186\/s13023-020-01517-2","journal-title":"Orphanet J Rare Dis"},{"key":"3022_CR15","doi-asserted-by":"publisher","first-page":"1716","DOI":"10.1212\/WNL.0b013e3181e04325","volume":"74","author":"PB Crino","year":"2010","unstructured":"Crino PB, Aronica E, Baltuch G, Nathanson KL (2010) Biallelic TSC gene inactivation in tuberous sclerosis complex. Neurology 74:1716\u20131723. https:\/\/doi.org\/10.1212\/WNL.0b013e3181e04325","journal-title":"Neurology"},{"key":"3022_CR16","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1016\/s1474-4422(15)00069-1","volume":"14","author":"P Curatolo","year":"2015","unstructured":"Curatolo P, Moavero R, de Vries PJ (2015) Neurological and neuropsychiatric aspects of tuberous sclerosis complex. Lancet Neurol 14:733\u2013745. https:\/\/doi.org\/10.1016\/s1474-4422(15)00069-1","journal-title":"Lancet Neurol"},{"key":"3022_CR17","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-018-0901-8","volume":"13","author":"PJ de Vries","year":"2018","unstructured":"de Vries PJ, Belousova E, Benedik MP, Carter T, Cottin V, Curatolo P et al (2018) TSC-associated neuropsychiatric disorders (TAND): findings from the TOSCA natural history study. Orphanet J Rare Dis 13:157. https:\/\/doi.org\/10.1186\/s13023-018-0901-8","journal-title":"Orphanet J Rare Dis"},{"key":"3022_CR18","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-018-0870-y","volume":"13","author":"D Ebrahimi-Fakhari","year":"2018","unstructured":"Ebrahimi-Fakhari D, Mann LL, Poryo M, Graf N, von Kries R, Heinrich B et al (2018) Incidence of tuberous sclerosis and age at first diagnosis: new data and emerging trends from a national, prospective surveillance study. Orphanet J Rare Dis 13:117. https:\/\/doi.org\/10.1186\/s13023-018-0870-y","journal-title":"Orphanet J Rare Dis"},{"key":"3022_CR19","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1016\/j.celrep.2016.09.054","volume":"17","author":"D Ebrahimi-Fakhari","year":"2016","unstructured":"Ebrahimi-Fakhari D, Saffari A, Wahlster L, Di Nardo A, Turner D, Lewis TL Jr. et al (2016) Impaired mitochondrial dynamics and mitophagy in neuronal models of Tuberous Sclerosis Complex. Cell Rep 17:1053\u20131070. https:\/\/doi.org\/10.1016\/j.celrep.2016.09.054","journal-title":"Cell Rep"},{"key":"3022_CR20","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1002\/glia.10324","volume":"46","author":"KC Ess","year":"2004","unstructured":"Ess KC, Uhlmann EJ, Li W, Li H, Declue JE, Crino PB et al (2004) Expression profiling in tuberous sclerosis complex (TSC) knockout mouse astrocytes to characterize human TSC brain pathology. Glia 46:28\u201340. https:\/\/doi.org\/10.1002\/glia.10324","journal-title":"Glia"},{"key":"3022_CR21","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2020.00039","volume":"14","author":"DM Feliciano","year":"2020","unstructured":"Feliciano DM (2020) The neurodevelopmental pathogenesis of tuberous sclerosis complex (TSC). Front Neuroanat 14:39. https:\/\/doi.org\/10.3389\/fnana.2020.00039","journal-title":"Front Neuroanat"},{"key":"3022_CR22","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1002\/humu.21438","volume":"32","author":"IF Fokkema","year":"2011","unstructured":"Fokkema IF, Taschner PE, Schaafsma GC, Celli J, Laros JF, den Dunnen JT (2011) LOVD v.2.0: the next generation in gene variant databases. Hum Mutat 32:557\u2013563. https:\/\/doi.org\/10.1002\/humu.21438","journal-title":"Hum Mutat"},{"key":"3022_CR23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0158476","volume":"11","author":"DN Franz","year":"2016","unstructured":"Franz DN, Belousova E, Sparagana S, Bebin EM, Frost MD, Kuperman R et al (2016) Long-term use of Everolimus in patients with tuberous sclerosis complex: final results from the EXIST-1 study. PLoS ONE 11:e0158476. https:\/\/doi.org\/10.1371\/journal.pone.0158476","journal-title":"PLoS ONE"},{"key":"3022_CR24","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1007\/s00439-016-1683-5","volume":"135","author":"T Geuens","year":"2016","unstructured":"Geuens T, Bouhy D, Timmerman V (2016) The hnRNP family: insights into their role in health and disease. Hum Genet 135:851\u2013867. https:\/\/doi.org\/10.1007\/s00439-016-1683-5","journal-title":"Hum Genet"},{"key":"3022_CR25","doi-asserted-by":"publisher","first-page":"2639","DOI":"10.1038\/s41436-019-0562-6","volume":"21","author":"K Giannikou","year":"2019","unstructured":"Giannikou K, Lasseter KD, Grevelink JM, Tyburczy ME, Dies KA, Zhu Z et al (2019) Low-level mosaicism in tuberous sclerosis complex: prevalence, clinical features, and risk of disease transmission. Genet Med 21:2639\u20132643. https:\/\/doi.org\/10.1038\/s41436-019-0562-6","journal-title":"Genet Med"},{"key":"3022_CR26","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1038\/s41379-020-00659-9","volume":"34","author":"K Giannikou","year":"2021","unstructured":"Giannikou K, Zhu Z, Kim J, Winden KD, Tyburczy ME, Marron D et al (2021) Subependymal giant cell astrocytomas are characterized by mTORC1 hyperactivation, a very low somatic mutation rate, and a unique gene expression profile. Mod Pathol 34:264\u2013279. https:\/\/doi.org\/10.1038\/s41379-020-00659-9","journal-title":"Mod Pathol"},{"key":"3022_CR27","doi-asserted-by":"publisher","DOI":"10.1101\/416511","author":"M Gierlinski","year":"2018","unstructured":"Gierlinski M, Gastaldello F, Cole C, Barton GJ (2018) An R package for downstream analysis of output. BioRxiv. https:\/\/doi.org\/10.1101\/416511","journal-title":"BioRxiv"},{"key":"3022_CR28","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2022.1005631","volume":"15","author":"M Girodengo","year":"2022","unstructured":"Girodengo M, Ultanir SK, Bateman JM (2022) Mechanistic target of rapamycin signaling in human nervous system development and disease. Front Mol Neurosci 15:1005631. https:\/\/doi.org\/10.3389\/fnmol.2022.1005631","journal-title":"Front Mol Neurosci"},{"key":"3022_CR29","doi-asserted-by":"publisher","first-page":"3923","DOI":"10.1172\/jci43552","volume":"120","author":"RW Goehe","year":"2010","unstructured":"Goehe RW, Shultz JC, Murudkar C, Usanovic S, Lamour NF, Massey DH et al (2010) hnRNP L regulates the tumorigenic capacity of lung cancer xenografts in mice via caspase-9 pre-mRNA processing. J Clin Invest 120:3923\u20133939. https:\/\/doi.org\/10.1172\/jci43552","journal-title":"J Clin Invest"},{"key":"3022_CR30","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1016\/j.cell.2017.06.037","volume":"170","author":"S Gueroussov","year":"2017","unstructured":"Gueroussov S, Weatheritt RJ, O\u2019Hanlon D, Lin ZY, Narula A, Gingras AC et al (2017) Regulatory expansion in mammals of multivalent hnRNP assemblies that globally control alternative splicing. Cell 170:324-339.e323. https:\/\/doi.org\/10.1016\/j.cell.2017.06.037","journal-title":"Cell"},{"key":"3022_CR31","doi-asserted-by":"publisher","first-page":"18090","DOI":"10.1074\/jbc.M011396200","volume":"276","author":"H Habelhah","year":"2001","unstructured":"Habelhah H, Shah K, Huang L, Burlingame AL, Shokat KM, Ronai Z (2001) Identification of new JNK substrate using ATP pocket mutant JNK and a corresponding ATP analogue. J Biol Chem 276:18090\u201318095. https:\/\/doi.org\/10.1074\/jbc.M011396200","journal-title":"J Biol Chem"},{"key":"3022_CR32","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1038\/35060131","volume":"3","author":"H Habelhah","year":"2001","unstructured":"Habelhah H, Shah K, Huang L, Ostareck-Lederer A, Burlingame AL, Shokat KM et al (2001) ERK phosphorylation drives cytoplasmic accumulation of hnRNP-K and inhibition of mRNA translation. Nat Cell Biol 3:325\u2013330. https:\/\/doi.org\/10.1038\/35060131","journal-title":"Nat Cell Biol"},{"key":"3022_CR33","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.celrep.2013.09.017","volume":"5","author":"NW Hartman","year":"2013","unstructured":"Hartman NW, Lin TV, Zhang L, Paquelet GE, Feliciano DM, Bordey A (2013) mTORC1 targets the translational repressor 4E-BP2, but not S6 kinase 1\/2, to regulate neural stem cell self-renewal in vivo. Cell Rep 5:433\u2013444. https:\/\/doi.org\/10.1016\/j.celrep.2013.09.017","journal-title":"Cell Rep"},{"key":"3022_CR34","first-page":"400","volume":"59","author":"EP Henske","year":"1996","unstructured":"Henske EP, Scheithauer BW, Short MP, Wollmann R, Nahmias J, Hornigold N et al (1996) Allelic loss is frequent in tuberous sclerosis kidney lesions but rare in brain lesions. Am J Hum Genet 59:400\u2013406","journal-title":"Am J Hum Genet"},{"key":"3022_CR35","first-page":"1639","volume":"151","author":"EP Henske","year":"1997","unstructured":"Henske EP, Wessner LL, Golden J, Scheithauer BW, Vortmeyer AO, Zhuang Z et al (1997) Loss of tuberin in both subependymal giant cell astrocytomas and angiomyolipomas supports a two-hit model for the pathogenesis of tuberous sclerosis tumors. Am J Pathol 151:1639\u20131647","journal-title":"Am J Pathol"},{"key":"3022_CR36","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1126\/science.1199498","volume":"332","author":"PP Hsu","year":"2011","unstructured":"Hsu PP, Kang SA, Rameseder J, Zhang Y, Ottina KA, Lim D et al (2011) The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science 332:1317\u20131322. https:\/\/doi.org\/10.1126\/science.1199498","journal-title":"Science"},{"key":"3022_CR37","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00821","volume":"10","author":"AC Jansen","year":"2019","unstructured":"Jansen AC, Belousova E, Benedik MP, Carter T, Cottin V, Curatolo P et al (2019) Newly diagnosed and growing Subependymal Giant Cell Astrocytoma in adults with Tuberous Sclerosis Complex: results from the International TOSCA Study. Front Neurol 10:821. https:\/\/doi.org\/10.3389\/fneur.2019.00821","journal-title":"Front Neurol"},{"key":"3022_CR38","doi-asserted-by":"publisher","first-page":"4244","DOI":"10.1021\/acs.jproteome.7b00610","volume":"16","author":"X Jiang","year":"2017","unstructured":"Jiang X, Bomgarden R, Brown J, Drew DL, Robitaille AM, Viner R et al (2017) Sensitive and accurate quantitation of phosphopeptides using TMT isobaric labeling technique. J Proteome Res 16:4244\u20134252. https:\/\/doi.org\/10.1021\/acs.jproteome.7b00610","journal-title":"J Proteome Res"},{"key":"3022_CR39","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","volume":"581","author":"KJ Karczewski","year":"2020","unstructured":"Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alf\u00f6ldi J, Wang Q et al (2020) The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 581:434\u2013443. https:\/\/doi.org\/10.1038\/s41586-020-2308-7","journal-title":"Nature"},{"key":"3022_CR40","doi-asserted-by":"publisher","first-page":"15340","DOI":"10.1074\/jbc.M500214200","volume":"280","author":"T Kattapuram","year":"2005","unstructured":"Kattapuram T, Yang S, Maki JL, Stone JR (2005) Protein kinase CK1alpha regulates mRNA binding by heterogeneous nuclear ribonucleoprotein C in response to physiologic levels of hydrogen peroxide. J Biol Chem 280:15340\u201315347. https:\/\/doi.org\/10.1074\/jbc.M500214200","journal-title":"J Biol Chem"},{"key":"3022_CR41","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1016\/j.ajhg.2023.04.002","volume":"110","author":"K Klonowska","year":"2023","unstructured":"Klonowska K, Giannikou K, Grevelink JM, Boeszoermenyi B, Thorner AR, Herbert ZT et al (2023) Comprehensive genetic and phenotype analysis of 95 individuals with mosaic tuberous sclerosis complex. Am J Hum Genet 110:979\u2013988. https:\/\/doi.org\/10.1016\/j.ajhg.2023.04.002","journal-title":"Am J Hum Genet"},{"key":"3022_CR42","doi-asserted-by":"publisher","DOI":"10.1172\/jci155858","author":"K Klonowska","year":"2022","unstructured":"Klonowska K, Grevelink JM, Giannikou K, Ogorek BA, Herbert ZT, Thorner AR et al (2022) Ultrasensitive profiling of UV-induced mutations identifies thousands of subclinical facial tumors in tuberous sclerosis complex. J Clin Invest. https:\/\/doi.org\/10.1172\/jci155858","journal-title":"J Clin Invest"},{"key":"3022_CR43","doi-asserted-by":"publisher","first-page":"2811","DOI":"10.1093\/bioinformatics\/btab051","volume":"37","author":"M Lefter","year":"2021","unstructured":"Lefter M, Vis JK, Vermaat M, den Dunnen JT, Taschner PEM, Laros JFJ (2021) Mutalyzer 2: next generation HGVS nomenclature checker. Bioinformatics (Oxford, England) 37:2811\u20132817. https:\/\/doi.org\/10.1093\/bioinformatics\/btab051","journal-title":"Bioinformatics (Oxford, England)"},{"key":"3022_CR44","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-024-02198-7","volume":"10","author":"B Li","year":"2024","unstructured":"Li B, Wen M, Gao F, Wang Y, Wei G, Duan Y (2024) Regulation of HNRNP family by post-translational modifications in cancer. Cell Death Discov 10:427. https:\/\/doi.org\/10.1038\/s41420-024-02198-7","journal-title":"Cell Death Discov"},{"key":"3022_CR45","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1038\/sj.npp.1300112","volume":"28","author":"J Li","year":"2003","unstructured":"Li J, Gould TD, Yuan P, Manji HK, Chen G (2003) Post-mortem interval effects on the phosphorylation of signaling proteins. Neuropsychopharmacol 28:1017\u20131025. https:\/\/doi.org\/10.1038\/sj.npp.1300112","journal-title":"Neuropsychopharmacol"},{"key":"3022_CR46","doi-asserted-by":"publisher","first-page":"11330","DOI":"10.1073\/pnas.1605740113","volume":"113","author":"TV Lin","year":"2016","unstructured":"Lin TV, Hsieh L, Kimura T, Malone TJ, Bordey A (2016) Normalizing translation through 4E-BP prevents mTOR-driven cortical mislamination and ameliorates aberrant neuron integration. Proc Natl Acad Sci U S A 113:11330\u201311335. https:\/\/doi.org\/10.1073\/pnas.1605740113","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3022_CR47","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/s41580-019-0199-y","volume":"21","author":"GY Liu","year":"2020","unstructured":"Liu GY, Sabatini DM (2020) mTOR at the nexus of nutrition, growth, ageing and disease. Nat Rev Mol Cell Biol 21:183\u2013203. https:\/\/doi.org\/10.1038\/s41580-019-0199-y","journal-title":"Nat Rev Mol Cell Biol"},{"key":"3022_CR48","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-022-02266-0","volume":"17","author":"C Luo","year":"2022","unstructured":"Luo C, Ye WR, Shi W, Yin P, Chen C, He YB et al (2022) Perfect match: mTOR inhibitors and tuberous sclerosis complex. Orphanet J Rare Dis 17:106. https:\/\/doi.org\/10.1186\/s13023-022-02266-0","journal-title":"Orphanet J Rare Dis"},{"key":"3022_CR49","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.ydbio.2020.01.006","volume":"461","author":"KT Maierbrugger","year":"2020","unstructured":"Maierbrugger KT, Sousa-Nunes R, Bateman JM (2020) The mTOR pathway component Unkempt regulates neural stem cell and neural progenitor cell cycle in the Drosophila central nervous system. Dev Biol 461:55\u201365. https:\/\/doi.org\/10.1016\/j.ydbio.2020.01.006","journal-title":"Dev Biol"},{"key":"3022_CR50","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1016\/j.cels.2023.10.003","volume":"14","author":"A Makhmut","year":"2023","unstructured":"Makhmut A, Qin D, Fritzsche S, Nimo J, K\u00f6nig J, Coscia F (2023) A framework for ultra-low-input spatial tissue proteomics. Cell Syst 14:1002-1014.e1005. https:\/\/doi.org\/10.1016\/j.cels.2023.10.003","journal-title":"Cell Syst"},{"key":"3022_CR51","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-025-03740-1","volume":"20","author":"L Mantoan Ritter","year":"2025","unstructured":"Mantoan Ritter L, Annear NMP, Baple EL, Ben-Chaabane LY, Bodi I, Brosson L et al (2025) mTOR pathway diseases: challenges and opportunities from bench to bedside and the mTOR node. Orphanet J Rare Dis 20:256. https:\/\/doi.org\/10.1186\/s13023-025-03740-1","journal-title":"Orphanet J Rare Dis"},{"key":"3022_CR52","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15816","volume":"8","author":"KR Martin","year":"2017","unstructured":"Martin KR, Zhou W, Bowman MJ, Shih J, Au KS, Dittenhafer-Reed KE et al (2017) The genomic landscape of tuberous sclerosis complex. Nat Commun 8:15816. https:\/\/doi.org\/10.1038\/ncomms15816","journal-title":"Nat Commun"},{"key":"3022_CR53","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41304-8","volume":"14","author":"SR Mihaylov","year":"2023","unstructured":"Mihaylov SR, Castelli LM, Lin YH, G\u00fcl A, Soni N, Hastings C et al (2023) The master energy homeostasis regulator PGC-1\u03b1 exhibits an mRNA nuclear export function. Nat Commun 14:5496. https:\/\/doi.org\/10.1038\/s41467-023-41304-8","journal-title":"Nat Commun"},{"key":"3022_CR54","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1016\/S0387-7604(01)00304-7","volume":"23","author":"M Mizuguchi","year":"2001","unstructured":"Mizuguchi M, Takashima S (2001) Neuropathology of Tuberous Sclerosis. Brain Dev 23:508\u2013515","journal-title":"Brain Dev"},{"key":"3022_CR55","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0157396","volume":"11","author":"A M\u00fchlebner","year":"2016","unstructured":"M\u00fchlebner A, van Scheppingen J, Hulshof HM, Scholl T, Iyer AM, Anink JJ et al (2016) Novel histopathological patterns in cortical tubers of epilepsy surgery patients with Tuberous Sclerosis Complex. PLoS ONE 11:e0157396. https:\/\/doi.org\/10.1371\/journal.pone.0157396","journal-title":"PLoS ONE"},{"key":"3022_CR56","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1038\/nsmb.3140","volume":"23","author":"J Murn","year":"2016","unstructured":"Murn J, Teplova M, Zarnack K, Shi Y, Patel DJ (2016) Recognition of distinct RNA motifs by the clustered CCCH zinc fingers of neuronal protein Unkempt. Nat Struct Mol Biol 23:16\u201323. https:\/\/doi.org\/10.1038\/nsmb.3140","journal-title":"Nat Struct Mol Biol"},{"key":"3022_CR57","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1101\/gad.258483.115","volume":"29","author":"J Murn","year":"2015","unstructured":"Murn J, Zarnack K, Yang YJ, Durak O, Murphy EA, Cheloufi S et al (2015) Control of a neuronal morphology program by an RNA-binding zinc finger protein, Unkempt. Genes Dev 29:501\u2013512. https:\/\/doi.org\/10.1101\/gad.258483.115","journal-title":"Genes Dev"},{"key":"3022_CR58","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1086\/321972","volume":"69","author":"Y Niida","year":"2001","unstructured":"Niida Y, Stemmer-Rachamimov AO, Logrip M, Tapon D, Perez R, Kwiatkowski DJ et al (2001) Survey of somatic mutations in tuberous sclerosis complex (TSC) hamartomas suggests different genetic mechanisms for pathogenesis of TSC lesions. Am J Hum Genet 69:493\u2013503. https:\/\/doi.org\/10.1086\/321972","journal-title":"Am J Hum Genet"},{"key":"3022_CR59","doi-asserted-by":"publisher","DOI":"10.1101\/2024.10.07.617121","author":"W Niu","year":"2024","unstructured":"Niu W, Yu S, Li X, Wang Z, Chen R, Michalski C et al (2024) Longitudinal multi-omics reveals pathogenic TSC2 variants disrupt developmental trajectories of human cortical organoids derived from Tuberous Sclerosis Complex. BioRxiv. https:\/\/doi.org\/10.1101\/2024.10.07.617121","journal-title":"BioRxiv"},{"key":"3022_CR60","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.pediatrneurol.2021.07.011","volume":"123","author":"H Northrup","year":"2021","unstructured":"Northrup H, Aronow ME, Bebin EM, Bissler J, Darling TN, de Vries PJ et al (2021) Updated International tuberous sclerosis complex diagnostic criteria and surveillance and management recommendations. Pediatr Neurol 123:50\u201366. https:\/\/doi.org\/10.1016\/j.pediatrneurol.2021.07.011","journal-title":"Pediatr Neurol"},{"key":"3022_CR61","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.pediatrneurol.2013.08.001","volume":"49","author":"H Northrup","year":"2013","unstructured":"Northrup H, Krueger DA (2013) Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 Iinternational tuberous sclerosis complex consensus conference. Pediatr Neurol 49:243\u2013254. https:\/\/doi.org\/10.1016\/j.pediatrneurol.2013.08.001","journal-title":"Pediatr Neurol"},{"key":"3022_CR62","doi-asserted-by":"publisher","first-page":"1490","DOI":"10.1016\/s0140-6736(05)78872-3","volume":"351","author":"FJ O\u2019Callaghan","year":"1998","unstructured":"O\u2019Callaghan FJ, Shiell AW, Osborne JP, Martyn CN (1998) Prevalence of tuberous sclerosis estimated by capture-recapture analysis. Lancet 351:1490. https:\/\/doi.org\/10.1016\/s0140-6736(05)78872-3","journal-title":"Lancet"},{"key":"3022_CR63","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1038\/s41436-020-0823-4","volume":"22","author":"B Og\u00f3rek","year":"2020","unstructured":"Og\u00f3rek B, Hamieh L, Hulshof HM, Lasseter K, Klonowska K, Kuijf H et al (2020) TSC2 pathogenic variants are predictive of severe clinical manifestations in TSC infants: results of the EPISTOP study. Genet Med 22:1489\u20131497. https:\/\/doi.org\/10.1038\/s41436-020-0823-4","journal-title":"Genet Med"},{"key":"3022_CR64","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021405","volume":"6","author":"T Oka","year":"2011","unstructured":"Oka T, Tagawa K, Ito H, Okazawa H (2011) Dynamic changes of the phosphoproteome in postmortem mouse brains. PLoS ONE 6:e21405. https:\/\/doi.org\/10.1371\/journal.pone.0021405","journal-title":"PLoS ONE"},{"key":"3022_CR65","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1111\/j.1749-6632.2009.05117.x","volume":"1184","author":"KA Orlova","year":"2010","unstructured":"Orlova KA, Crino PB (2010) The tuberous sclerosis complex. Ann N Y Acad Sci 1184:87\u2013105. https:\/\/doi.org\/10.1111\/j.1749-6632.2009.05117.x","journal-title":"Ann N Y Acad Sci"},{"key":"3022_CR66","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.ajpath.2010.11.031","volume":"178","author":"WE Parker","year":"2011","unstructured":"Parker WE, Orlova KA, Heuer GG, Baybis M, Aronica E, Frost M et al (2011) Enhanced epidermal growth factor, hepatocyte growth factor, and vascular endothelial growth factor expression in tuberous sclerosis complex. Am J Pathol 178:296\u2013305. https:\/\/doi.org\/10.1016\/j.ajpath.2010.11.031","journal-title":"Am J Pathol"},{"key":"3022_CR67","doi-asserted-by":"publisher","first-page":"D543","DOI":"10.1093\/nar\/gkae1011","volume":"53","author":"Y Perez-Riverol","year":"2025","unstructured":"Perez-Riverol Y, Bandla C, Kundu DJ, Kamatchinathan S, Bai J, Hewapathirana S et al (2025) The PRIDE database at 20 years: 2025 update. Nucleic Acids Res 53:D543-d553. https:\/\/doi.org\/10.1093\/nar\/gkae1011","journal-title":"Nucleic Acids Res"},{"key":"3022_CR68","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1007\/s00381-008-0681-x","volume":"24","author":"JH Phi","year":"2008","unstructured":"Phi JH, Park SH, Chae JH, Hong KH, Park SS, Kang JH et al (2008) Congenital subependymal giant cell astrocytoma: clinical considerations and expression of radial glial cell markers in giant cells. Childs Nerv Syst 24:1499\u20131503. https:\/\/doi.org\/10.1007\/s00381-008-0681-x","journal-title":"Childs Nerv Syst"},{"key":"3022_CR69","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1111\/j.1750-3639.2012.00616.x","volume":"23","author":"AS Prabowo","year":"2013","unstructured":"Prabowo AS, Anink JJ, Lammens M, Nellist M, van den Ouweland AM, Adle-Biassette H et al (2013) Fetal brain lesions in tuberous sclerosis complex: TORC1 activation and inflammation. Brain pathology (Zurich, Switzerland) 23:45\u201359. https:\/\/doi.org\/10.1111\/j.1750-3639.2012.00616.x","journal-title":"Brain pathology (Zurich, Switzerland)"},{"key":"3022_CR70","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1126\/science.1228771","volume":"339","author":"AM Robitaille","year":"2013","unstructured":"Robitaille AM, Christen S, Shimobayashi M, Cornu M, Fava LL, Moes S et al (2013) Quantitative phosphoproteomics reveal mTORC1 activates de novo pyrimidine synthesis. Science 339:1320\u20131323. https:\/\/doi.org\/10.1126\/science.1228771","journal-title":"Science"},{"key":"3022_CR71","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202201712","author":"F Ro\u015fianu","year":"2023","unstructured":"Ro\u015fianu F, Mihaylov SR, Eder N, Martiniuc A, Claxton S, Flynn HR et al (2023) Loss of NDR1\/2 kinases impairs endomembrane trafficking and autophagy leading to neurodegeneration. Life Sci Alliance. https:\/\/doi.org\/10.26508\/lsa.202201712","journal-title":"Life Sci Alliance"},{"key":"3022_CR72","doi-asserted-by":"publisher","first-page":"12483","DOI":"10.1093\/nar\/gku953","volume":"42","author":"R Roy","year":"2014","unstructured":"Roy R, Durie D, Li H, Liu BQ, Skehel JM, Mauri F et al (2014) hnRNPA1 couples nuclear export and translation of specific mRNAs downstream of FGF-2\/S6K2 signalling. Nucleic Acids Res 42:12483\u201312497. https:\/\/doi.org\/10.1093\/nar\/gku953","journal-title":"Nucleic Acids Res"},{"key":"3022_CR73","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1002\/uog.6367","volume":"34","author":"J Saada","year":"2009","unstructured":"Saada J, Hadj Rabia S, Fermont L, Le Bidois J, Bernardes LS, Martinovic J et al (2009) Prenatal diagnosis of cardiac rhabdomyomas: incidence of associated cerebral lesions of tuberous sclerosis complex. Ultrasound Obstet Gynecol 34:155\u2013159. https:\/\/doi.org\/10.1002\/uog.6367","journal-title":"Ultrasound Obstet Gynecol"},{"key":"3022_CR74","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1146\/annurev-genom-083118-015354","volume":"20","author":"CL Salussolia","year":"2019","unstructured":"Salussolia CL, Klonowska K, Kwiatkowski DJ, Sahin M (2019) Genetic etiologies, diagnosis, and treatment of tuberous sclerosis complex. Annu Rev Genomics Hum Genet 20:217\u2013240. https:\/\/doi.org\/10.1146\/annurev-genom-083118-015354","journal-title":"Annu Rev Genomics Hum Genet"},{"key":"3022_CR75","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD011272.pub3","author":"TH Sasongko","year":"2023","unstructured":"Sasongko TH, Kademane K, Chai Soon Hou S, Jocelyn TXY, Zabidi-Hussin Z (2023) Rapamycin and rapalogs for tuberous sclerosis complex. Cochrane Database Syst Rev. https:\/\/doi.org\/10.1002\/14651858.CD011272.pub3","journal-title":"Cochrane Database Syst Rev"},{"key":"3022_CR76","doi-asserted-by":"publisher","first-page":"2042","DOI":"10.1074\/mcp.M114.045807","volume":"14","author":"JJ Schwarz","year":"2015","unstructured":"Schwarz JJ, Wiese H, T\u00f6lle RC, Zarei M, Dengjel J, Warscheid B et al (2015) Functional proteomics identifies Acinus L as a direct insulin- and amino acid-dependent mammalian target of Rapamycin complex 1 (mTORC1) substrate. Mol Cell Proteomics 14:2042\u20132055. https:\/\/doi.org\/10.1074\/mcp.M114.045807","journal-title":"Mol Cell Proteomics"},{"key":"3022_CR77","doi-asserted-by":"publisher","first-page":"2026","DOI":"10.1021\/acs.proteome.9b00860","volume":"19","author":"DK Schweppe","year":"2020","unstructured":"Schweppe DK, Eng JK, Yu Q, Bailey D, Rad R, Navarrete-Perea J et al (2020) Full-featured, real-time database searching platform enables fast and accurate multiplexed quantitative proteomics. J Proteome Res 19:2026\u20132034. https:\/\/doi.org\/10.1021\/acs.proteome.9b00860","journal-title":"J Proteome Res"},{"key":"3022_CR78","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1136\/jmg.33.11.962","volume":"33","author":"T Sepp","year":"1996","unstructured":"Sepp T, Yates JR, Green AJ (1996) Loss of heterozygosity in tuberous sclerosis hamartomas. J Med Genet 33:962\u2013964. https:\/\/doi.org\/10.1136\/jmg.33.11.962","journal-title":"J Med Genet"},{"key":"3022_CR79","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47449-4","volume":"15","author":"K Shah","year":"2024","unstructured":"Shah K, He S, Turner DJ, Corbo J, Rebbani K, Dominguez D et al (2024) Regulation by the RNA-binding protein Unkempt at its effector interface. Nat Commun 15:3159. https:\/\/doi.org\/10.1038\/s41467-024-47449-4","journal-title":"Nat Commun"},{"key":"3022_CR80","doi-asserted-by":"publisher","first-page":"E5593","DOI":"10.1073\/pnas.1419161111","volume":"111","author":"S Shen","year":"2014","unstructured":"Shen S, Park JW, Lu ZX, Lin L, Henry MD, Wu YN et al (2014) rMATS: robust and flexible detection of differential alternative splicing from replicate RNA-Seq data. Proc Natl Acad Sci U S A 111:E5593-5601. https:\/\/doi.org\/10.1073\/pnas.1419161111","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3022_CR81","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/bf01403693","volume":"26","author":"P Sonigo","year":"1996","unstructured":"Sonigo P, Elmaleh A, Fermont L, Delezo\u00edde AL, Mirlesse V, Brunelle F (1996) Prenatal MRI diagnosis of fetal cerebral tuberous sclerosis. Pediatr Radiol 26:1\u20134. https:\/\/doi.org\/10.1007\/bf01403693","journal-title":"Pediatr Radiol"},{"key":"3022_CR82","doi-asserted-by":"publisher","first-page":"4102","DOI":"10.1093\/bioinformatics\/bty403","volume":"34","author":"AD Staszowska","year":"2018","unstructured":"Staszowska AD, Fox-Roberts P, Hirvonen LM, Peddie CJ, Collinson LM, Jones GE et al (2018) The R\u00e9nyi divergence enables accurate and precise cluster analysis for localization microscopy. Bioinformatics 34:4102\u20134111. https:\/\/doi.org\/10.1093\/bioinformatics\/bty403","journal-title":"Bioinformatics"},{"key":"3022_CR83","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1021\/bi0268091","volume":"42","author":"JR Stone","year":"2003","unstructured":"Stone JR, Maki JL, Collins T (2003) Basal and hydrogen peroxide stimulated sites of phosphorylation in heterogeneous nuclear ribonucleoprotein C1\/C2. Biochemistry 42:1301\u20131308. https:\/\/doi.org\/10.1021\/bi0268091","journal-title":"Biochemistry"},{"key":"3022_CR84","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1039\/c9mo00149b","volume":"16","author":"AJ Storey","year":"2020","unstructured":"Storey AJ, Naceanceno KS, Lan RS, Washam CL, Orr LM, Mackintosh SG et al (2020) ProteoViz: a tool for the analysis and interactive visualization of phosphoproteomics data. Mol Omics 16:316\u2013326. https:\/\/doi.org\/10.1039\/c9mo00149b","journal-title":"Mol Omics"},{"key":"3022_CR85","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.seizure.2021.06.027","volume":"91","author":"A Strzelczyk","year":"2021","unstructured":"Strzelczyk A, Rosenow F, Z\u00f6llner JP, Simon A, Wyatt G, Holland R et al (2021) Epidemiology, healthcare resource use, and mortality in patients with tuberous sclerosis complex: a population-based study on German health insurance data. Seizure 91:287\u2013295. https:\/\/doi.org\/10.1016\/j.seizure.2021.06.027","journal-title":"Seizure"},{"key":"3022_CR86","doi-asserted-by":"publisher","first-page":"7323","DOI":"10.3892\/ol.2017.7085","volume":"14","author":"Y Sun","year":"2017","unstructured":"Sun Y, Luo M, Chang G, Ren W, Wu K, Li X et al (2017) Phosphorylation of Ser6 in hnRNPA1 by S6K2 regulates glucose metabolism and cell growth in colorectal cancer. Oncol Lett 14:7323\u20137331. https:\/\/doi.org\/10.3892\/ol.2017.7085","journal-title":"Oncol Lett"},{"key":"3022_CR87","doi-asserted-by":"publisher","first-page":"D607","DOI":"10.1093\/nar\/gky1131","volume":"47","author":"D Szklarczyk","year":"2019","unstructured":"Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J et al (2019) STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 47:D607-d613. https:\/\/doi.org\/10.1093\/nar\/gky1131","journal-title":"Nucleic Acids Res"},{"key":"3022_CR88","doi-asserted-by":"publisher","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","volume":"51","author":"D Szklarczyk","year":"2023","unstructured":"Szklarczyk D, Kirsch R, Koutrouli M, Nastou K, Mehryary F, Hachilif R et al (2023) The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res 51:D638-d646. https:\/\/doi.org\/10.1093\/nar\/gkac1000","journal-title":"Nucleic Acids Res"},{"key":"3022_CR89","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.semcdb.2016.01.040","volume":"52","author":"AR Tee","year":"2016","unstructured":"Tee AR, Sampson JR, Pal DK, Bateman JM (2016) The role of mTOR signalling in neurogenesis, insights from tuberous sclerosis complex. Semin Cell Dev Biol 52:12\u201320. https:\/\/doi.org\/10.1016\/j.semcdb.2016.01.040","journal-title":"Semin Cell Dev Biol"},{"key":"3022_CR90","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-56335-6","volume":"16","author":"M Turewicz","year":"2025","unstructured":"Turewicz M, Skagen C, Hartwig S, Majda S, Thedinga K, Herwig R et al (2025) Temporal phosphoproteomics reveals circuitry of phased propagation in insulin signaling. Nat Commun 16:1570. https:\/\/doi.org\/10.1038\/s41467-025-56335-6","journal-title":"Nat Commun"},{"key":"3022_CR91","doi-asserted-by":"publisher","first-page":"1878","DOI":"10.2353\/ajpath.2010.090950","volume":"176","author":"ME Tyburczy","year":"2010","unstructured":"Tyburczy ME, Kotulska K, Pokarowski P, Mieczkowski J, Kucharska J, Grajkowska W et al (2010) Novel proteins regulated by mTOR in subependymal giant cell astrocytomas of patients with tuberous sclerosis complex and new therapeutic implications. Am J Pathol 176:1878\u20131890. https:\/\/doi.org\/10.2353\/ajpath.2010.090950","journal-title":"Am J Pathol"},{"key":"3022_CR92","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.molcel.2019.09.017","volume":"76","author":"J Ule","year":"2019","unstructured":"Ule J, Blencowe BJ (2019) Alternative splicing regulatory networks: functions, mechanisms, and evolution. Mol Cell 76:329\u2013345. https:\/\/doi.org\/10.1016\/j.molcel.2019.09.017","journal-title":"Mol Cell"},{"key":"3022_CR93","doi-asserted-by":"publisher","first-page":"2151","DOI":"10.1021\/acs.proteome.0c00977","volume":"20","author":"J Van Houtven","year":"2021","unstructured":"Van Houtven J, Hooyberghs J, Laukens K, Valkenborg D (2021) CONSTANd: an efficient normalization method for relative quantification in small- and large-scale omics experiments in R BioConductor and Python. J Proteome Res 20:2151\u20132156. https:\/\/doi.org\/10.1021\/acs.proteome.0c00977","journal-title":"J Proteome Res"},{"key":"3022_CR94","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-95286-y","volume":"11","author":"E Vinsland","year":"2021","unstructured":"Vinsland E, Baskaran P, Mihaylov SR, Hobbs C, Wood H, Bouybayoune I et al (2021) The zinc finger\/RING domain protein Unkempt regulates cognitive flexibility. Sci Rep 11:16299. https:\/\/doi.org\/10.1038\/s41598-021-95286-y","journal-title":"Sci Rep"},{"key":"3022_CR95","doi-asserted-by":"publisher","first-page":"4469","DOI":"10.1093\/bioinformatics\/btz247","volume":"35","author":"K Vitting-Seerup","year":"2019","unstructured":"Vitting-Seerup K, Sandelin A (2019) IsoformSwitchAnalyzeR: analysis of changes in genome-wide patterns of alternative splicing and its functional consequences. Bioinformatics 35:4469\u20134471. https:\/\/doi.org\/10.1093\/bioinformatics\/btz247","journal-title":"Bioinformatics"},{"key":"3022_CR96","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1146\/annurev-biochem-091719-064225","volume":"89","author":"ME Wilkinson","year":"2020","unstructured":"Wilkinson ME, Charenton C, Nagai K (2020) RNA Splicing by the Spliceosome. Annu Rev Biochem 89:359\u2013388. https:\/\/doi.org\/10.1146\/annurev-biochem-091719-064225","journal-title":"Annu Rev Biochem"},{"key":"3022_CR97","doi-asserted-by":"publisher","first-page":"3497","DOI":"10.1074\/mcp.M113.037309","volume":"13","author":"JR Wi\u015bniewski","year":"2014","unstructured":"Wi\u015bniewski JR, Hein MY, Cox J, Mann M (2014) A \u201cproteomic ruler\u201d for protein copy number and concentration estimation without spike-in standards. Mol Cell Proteomics 13:3497\u20133506. https:\/\/doi.org\/10.1074\/mcp.M113.037309","journal-title":"Mol Cell Proteomics"},{"key":"3022_CR98","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/s004010050587","volume":"93","author":"HK Wolf","year":"1997","unstructured":"Wolf HK, Normann S, Green AJ, von Bakel I, Bl\u00fcmcke I, Pietsch T et al (1997) Tuberous sclerosis-like lesions in epileptogenic human neocortex lack allelic loss at the TSC1 and TSC2 regions. Acta Neuropathol 93:93\u201396. https:\/\/doi.org\/10.1007\/s004010050587","journal-title":"Acta Neuropathol"},{"key":"3022_CR99","doi-asserted-by":"publisher","first-page":"D1196","DOI":"10.1093\/nar\/gkac955","volume":"51","author":"S Wu","year":"2023","unstructured":"Wu S, Huang Y, Zhang M, Gong Z, Wang G, Zheng X et al (2023) ASCancer Atlas: a comprehensive knowledgebase of alternative splicing in human cancers. Nucleic Acids Res 51:D1196-d1204. https:\/\/doi.org\/10.1093\/nar\/gkac955","journal-title":"Nucleic Acids Res"},{"key":"3022_CR100","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/s0387-7604(96)00079-4","volume":"19","author":"H Yamanouchi","year":"1997","unstructured":"Yamanouchi H, Ho M, Jay V, Becker LE (1997) Giant cells in cortical tubers in tuberous sclerosis showing synaptophysin-immunoreactive halos. Brain Develop 19:21\u201324. https:\/\/doi.org\/10.1016\/s0387-7604(96)00079-4","journal-title":"Brain Develop"},{"key":"3022_CR101","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1126\/science.1199484","volume":"332","author":"Y Yu","year":"2011","unstructured":"Yu Y, Yoon SO, Poulogiannis G, Yang Q, Ma XM, Villen J et al (2011) Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling. Science 332:1322\u20131326. https:\/\/doi.org\/10.1126\/science.1199484","journal-title":"Science"}],"container-title":["Acta Neuropathologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-026-03022-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00401-026-03022-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-026-03022-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T19:23:56Z","timestamp":1779305036000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00401-026-03022-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":101,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["3022"],"URL":"https:\/\/doi.org\/10.1007\/s00401-026-03022-5","relation":{},"ISSN":["1432-0533"],"issn-type":[{"value":"1432-0533","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,20]]},"assertion":[{"value":"4 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 April 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 April 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 May 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"60"}}