{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T19:36:12Z","timestamp":1783366572164,"version":"3.54.6"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/T04101X\/2"],"award-info":[{"award-number":["MR\/T04101X\/2"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common genetic cause of renal failure. Uncontrolled proliferation drives ADPKD, which manifests with cystic kidney enlargement. Yet, the mechanisms by which renal epithelial cells lose cell cycle control are largely unknown. To investigate this, we examined the expression and function of the Ankyrin Repeat and single KH Domain 1 (ANKHD1), which positively regulates proliferation in cancer, yet its role in ADPKD is unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We report elevated proliferation (Ki67 and Cyclin D1) in three independent mouse models of ADPKD, the\n                      <jats:italic>Pkd1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>nl\/nl<\/jats:italic>\n                      <\/jats:sup>\n                      , the\n                      <jats:italic>Pax8-cre; Pkd1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>del\/del<\/jats:italic>\n                      <\/jats:sup>\n                      and the\n                      <jats:italic>KSP-cre; Pkd1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>del\/del<\/jats:italic>\n                      <\/jats:sup>\n                      . We find that ANKHD1 protein localises in cyst lining cells of both aquaporin-1 and 2 (AQP1-AQP2) positive cysts. ANKHD1 knockdown in human cells or knockout in mouse tissues resulted in reduced proliferation, slower cystic growth in vitro and smaller kidneys in vivo; ultimately leading to improved renal function. Mechanistically, ANKHD1 binds to CDK4 and positively controls the Cyclin D1\/CDK4 pathway. ANKHD1-mediated enhancement of Cyclin D1\/CDK4 activity leads to increased retinoblastoma phosphorylation and proliferation, a mechanism that is p19-dependent but p21 independent.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We report a functional role for ANKHD1 in driving pathogenic proliferation in ADPKD via the Cyclin D1\/CDK4 axis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-025-06359-9","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T08:34:24Z","timestamp":1748853264000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["ANKHD1 promotes pathogenic proliferation in Autosomal Dominant Polycystic Kidney Disease via the Cyclin D1\/CDK4 pathway"],"prefix":"10.1186","volume":"23","author":[{"given":"Maria-Eirini","family":"Terzenidou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Foteini","family":"Patera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona M","family":"Macleod","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert C M","family":"Ong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Fragiadaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"issue":"9569","key":"6359_CR1","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1016\/S0140-6736(07)60601-1","volume":"14","author":"VE Torres","year":"2007","unstructured":"Torres VE, Harris PC, Pirson Y. Autosomal dominant polycystic kidney disease. Lancet. 2007;14(9569):1287\u2013301.","journal-title":"Lancet"},{"key":"6359_CR2","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1146\/annurev.med.60.101707.125712","volume":"60","author":"PC Harris","year":"2009","unstructured":"Harris PC, Torres VE. Polycystic kidney disease. Annu Rev Med. 2009;60:321\u201337.","journal-title":"Annu Rev Med"},{"issue":"9981","key":"6359_CR3","doi-asserted-by":"publisher","first-page":"1993","DOI":"10.1016\/S0140-6736(15)60907-2","volume":"16","author":"ACM Ong","year":"2015","unstructured":"Ong ACM, Devuyst O, Knebelmann B, Walz G, ERA-EDTA Working Group for Inherited Kidney Diseases. Autosomal dominant polycystic kidney disease: the changing face of clinical management. Lancet. 2015;16(9981):1993\u20132002.","journal-title":"Lancet"},{"issue":"6","key":"6359_CR4","first-page":"881","volume":"17","author":"TEPKD Consortium","year":"1994","unstructured":"Consortium TEPKD. The polycystic kidney disease 1 gene encodes a 14\u00a0kb transcript and Lies within a duplicated region on chromosome 16. Cell. 1994;17(6):881\u201394.","journal-title":"Cell"},{"issue":"5266","key":"6359_CR5","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1126\/science.272.5266.1339","volume":"31","author":"T Mochizuki","year":"1996","unstructured":"Mochizuki T, Wu G, Hayashi T, Xenophontos SL, Veldhuisen B, Saris JJ, Reynolds DM, Cai Y, Gabow PA, Pierides A, Kimberling WJ, Breuning MH, Deltas CC, Peters DJ, Somlo S. PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein. Science. 1996;31(5266):1339\u201342.","journal-title":"Science"},{"key":"6359_CR6","doi-asserted-by":"crossref","unstructured":"Ong ACM, Harris PC. A polycystin-centric view of cyst formation and disease: the polycystins revisited. Kidney Int 2015.","DOI":"10.1038\/ki.2015.207"},{"issue":"1","key":"6359_CR7","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1038\/s41572-018-0047-y","volume":"6","author":"C Bergmann","year":"2018","unstructured":"Bergmann C, Guay-Woodford LM, Harris PC, Horie S, Peters DJM, Torres VE. Polycystic kidney disease. Nat Rev Dis Primers. 2018;6(1):50.","journal-title":"Nat Rev Dis Primers"},{"issue":"12","key":"6359_CR8","doi-asserted-by":"publisher","first-page":"1490","DOI":"10.1038\/nm1675","volume":"13","author":"K Piontek","year":"2007","unstructured":"Piontek K, Menezes LF, Garcia-Gonzalez MA, Huso DL, Germino GG. A critical developmental switch defines the kinetics of kidney cyst formation after loss of Pkd1. Nat Med. 2007;13(12):1490\u20135.","journal-title":"Nat Med"},{"issue":"24","key":"6359_CR9","doi-asserted-by":"publisher","first-page":"3188","DOI":"10.1093\/hmg\/ddm299","volume":"16","author":"IS Lantinga-van Leeuwen","year":"2007","unstructured":"Lantinga-van Leeuwen IS, Leonhard WN, van der Wal A, Breuning MH, de Heer E, Peters DJ. Kidney-specific inactivation of the Pkd1 gene induces rapid cyst formation in developing kidneys and a slow onset of disease in adult mice. Hum Mol Genet. 2007;16(24):3188\u201396.","journal-title":"Hum Mol Genet"},{"issue":"11","key":"6359_CR10","doi-asserted-by":"publisher","first-page":"4257","DOI":"10.1172\/JCI64313","volume":"122","author":"K Hopp","year":"2012","unstructured":"Hopp K, Ward CJ, Hommerding CJ, Nasr SH, Tuan HF, Gainullin VG, Rossetti S, Torres VE, Harris PC. Functional polycystin-1 dosage governs autosomal dominant polycystic kidney disease severity. J Clin Invest. 2012;122(11):4257\u201373.","journal-title":"J Clin Invest"},{"issue":"6","key":"6359_CR11","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1681\/ASN.2012070650","volume":"24","author":"E Cornec-Le Gall","year":"2013","unstructured":"Cornec-Le Gall E, Audr\u00e9zet MP, Chen JM, Hourmant M, Morin MP, Perrichot R, Charasse C, Whebe B, Renaudineau E, Jousset P, Guillodo MP, Grall-Jezequel A, Saliou P, F\u00e9rec C, Le Meur Y. Type of PKD1 mutation influences renal outcome in ADPKD. J Am Soc Nephrol. 2013;24(6):1006\u201313.","journal-title":"J Am Soc Nephrol"},{"key":"6359_CR12","doi-asserted-by":"crossref","unstructured":"Lantinga-van Leeuwen IS, Dauwerse JG, Baelde HJ, Leonhard WN, van de Wal A, Ward CJ, Verbeek S, Deruiter MC, Breuning MH, de Heer E, Peters DJ. Lowering of Pkd1 expression is sufficient to cause polycystic kidney disease. Hum Mol Genet 2004.","DOI":"10.1093\/hmg\/ddh336"},{"key":"6359_CR13","doi-asserted-by":"crossref","unstructured":"Reeders ST. Multilocus polycystic disease. Nat Genet 1992, 235\u20137.","DOI":"10.1038\/ng0792-235"},{"issue":"6","key":"6359_CR14","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1016\/S0092-8674(00)81793-6","volume":"87","author":"F Qian","year":"1996","unstructured":"Qian F, Watnick TJ, Onuchic LF, Germino GG. The molecular basis of focal cyst formation in human autosomal dominant polycystic kidney disease type I. Cell. 1996;87(6):979\u201387.","journal-title":"Cell"},{"issue":"7","key":"6359_CR15","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.1681\/ASN.V1071524","volume":"10","author":"Y Pei","year":"1999","unstructured":"Pei Y, Watnick T, He N, Wang K, Liang Y, Parfrey P, Germino G, St George-Hyslop P. Somatic PKD2 mutations in individual kidney and liver cysts support a two-hit model of cystogenesis in type 2 autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 1999;10(7):1524\u20139.","journal-title":"J Am Soc Nephrol"},{"issue":"5","key":"6359_CR16","doi-asserted-by":"publisher","first-page":"166358","DOI":"10.1016\/j.bbadis.2022.166358","volume":"1868","author":"M Fragiadaki","year":"2022","unstructured":"Fragiadaki M. Lessons from MicroRNA biology: top key cellular drivers of autosomal dominant polycystic kidney disease. Biochim Biophys Acta. 2022;1868(5):166358.","journal-title":"Biochim Biophys Acta"},{"issue":"Suppl 1","key":"6359_CR17","doi-asserted-by":"publisher","first-page":"S55","DOI":"10.1097\/01.ASN.0000067652.51441.21","volume":"14","author":"JV Bonventre","year":"2003","unstructured":"Bonventre JV. Dedifferentiation and proliferation of surviving epithelial cells in acute renal failure. J Am Soc Nephrol. 2003;14(Suppl 1):S55\u201361.","journal-title":"J Am Soc Nephrol"},{"issue":"5","key":"6359_CR18","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1038\/ki.1987.121","volume":"31","author":"JJ Grantham","year":"1987","unstructured":"Grantham JJ, Geiser JL, Evan AP. Cyst formation and growth in autosomal dominant polycystic kidney disease. Kidney Int. 1987;31(5):1145\u201352.","journal-title":"Kidney Int"},{"issue":"2","key":"6359_CR19","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1038\/ng1076","volume":"33","author":"SM Nauli","year":"2003","unstructured":"Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X, Elia AE, Lu W, Brown EM, Quinn SJ, Ingber DE, Zhou J. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet. 2003;33(2):129\u201337.","journal-title":"Nat Genet"},{"key":"6359_CR20","unstructured":"Zhou JX, Li X. Apoptosis in polycystic kidney disease: from pathogenesis to treatment. Codon; Chap. 9 2015."},{"key":"6359_CR21","doi-asserted-by":"publisher","first-page":"109518","DOI":"10.1016\/j.cellsig.2019.109518","volume":"68","author":"KL Nowak","year":"2020","unstructured":"Nowak KL, Edelstein CL. Apoptosis and autophagy in polycystic kidney disease (PKD). Cell Signal. 2020;68:109518.","journal-title":"Cell Signal"},{"issue":"1","key":"6359_CR22","doi-asserted-by":"publisher","first-page":"4985","DOI":"10.1038\/s41598-018-23341-2","volume":"8","author":"LM Silva","year":"2018","unstructured":"Silva LM, Jacobs DT, Allard BA, Fields TA, Sharma M, Wallace DP, Tran PV. Inhibition of Hedgehog signaling suppresses proliferation and microcyst formation of human autosomal dominant polycystic kidney disease cells. Sci Rep. 2018;8(1):4985.","journal-title":"Sci Rep"},{"issue":"1","key":"6359_CR23","doi-asserted-by":"publisher","first-page":"4320","DOI":"10.1038\/s41467-020-18104-5","volume":"11","author":"I Cabrita","year":"2020","unstructured":"Cabrita I, Kraus A, Scholz JK, Skoczynski K, Schreiber R, Kunzelmann K, Buchholz B. Cyst growth in ADPKD is prevented by Pharmacological and genetic Inhibition of TMEM16A in vivo. Nat Commun. 2020;11(1):4320.","journal-title":"Nat Commun"},{"issue":"1","key":"6359_CR24","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1681\/ASN.2020040511","volume":"32","author":"C Zhang","year":"2021","unstructured":"Zhang C, Balbo B, Ma M, Zhao J, Tian X, Kluger Y, Somlo S. Cyclin-Dependent kinase 1 activity is a driver of cyst growth in polycystic kidney disease. J Am Soc Nephrol. 2021;32(1):41\u201351.","journal-title":"J Am Soc Nephrol"},{"key":"6359_CR25","unstructured":"Harris PC, Torres VE. Polycystic Kidney Disease, Autosomal Dominant. GeneReviews [Internet] 2022, 1993\u20132024."},{"issue":"14","key":"6359_CR26","doi-asserted-by":"publisher","first-page":"5466","DOI":"10.1073\/pnas.0509694103","volume":"103","author":"JM Shillingford","year":"2006","unstructured":"Shillingford JM, Murcia NS, Larson CH, Low SH, Hedgepeth R, Brown N, Flask CA, Novick AC, Goldfarb DA, Kramer-Zucker A, Walz G, Piontek KB, Germino GG, Weimbs T. The mTOR pathway is regulated by polycystin-1, and its Inhibition reverses renal cystogenesis in polycystic kidney disease. Proc Natl Acad Sci U S A. 2006;103(14):5466\u201371.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"6359_CR27","doi-asserted-by":"publisher","first-page":"F551","DOI":"10.1152\/ajprenal.00218.2014","volume":"307","author":"M Beck Gooz","year":"2014","unstructured":"Beck Gooz M, Maldonado EN, Dang Y, Amria MY, Higashiyama S, Abboud HE, Lemasters JJ, Bell PD. ADAM17 promotes proliferation of collecting duct kidney epithelial cells through ERK activation and increased Glycolysis in polycystic kidney disease. Am J Physiol Ren Physiol. 2014;307(5):F551\u20139.","journal-title":"Am J Physiol Ren Physiol"},{"issue":"1","key":"6359_CR28","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1681\/ASN.2013040398","volume":"25","author":"VE Torres","year":"2014","unstructured":"Torres VE, Harris PC. Strategies targeting cAMP signaling in the treatment of polycystic kidney disease. J Am Soc Nephrol. 2014;25(1):18\u201332.","journal-title":"J Am Soc Nephrol"},{"issue":"6","key":"6359_CR29","doi-asserted-by":"publisher","first-page":"eaaw3593","DOI":"10.1126\/sciadv.aaw3593","volume":"5","author":"Y Sun","year":"2019","unstructured":"Sun Y, Liu Z, Cao X, Lu Y, Mi Z, He C, Liu J, Zheng Z, Li MJ, Li T, Xu D, Wu M, Cao Y, Li Y, Yang B, Mei C, Zhang L, Chen Y. Activation of P-TEFb by cAMP-PKA signaling in autosomal dominant polycystic kidney disease. Sci Adv. 2019;5(6):eaaw3593.","journal-title":"Sci Adv"},{"issue":"1","key":"6359_CR30","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1002\/path.2856","volume":"224","author":"H Happ\u00e9","year":"2011","unstructured":"Happ\u00e9 H, van der Wal AM, Leonhard WN, Kunnen SJ, Breuning MH, de Heer E, Peters DJ. Altered Hippo signalling in polycystic kidney disease. J Pathol. 2011;224(1):133\u201342.","journal-title":"J Pathol"},{"key":"6359_CR31","doi-asserted-by":"publisher","first-page":"811","DOI":"10.3389\/fcell.2020.00811","volume":"8","author":"AW Shen","year":"2020","unstructured":"Shen AW, Fu LL, Lin L, Sun B, Song DX, Wang WT, Wang YH, Yin PR, Yu SQ. SNX9 inhibits cell proliferation and cyst development in autosomal dominant polycystic kidney disease via activation of the Hippo-YAP signaling pathway. Front Cell Dev Biol. 2020;8:811.","journal-title":"Front Cell Dev Biol"},{"issue":"2","key":"6359_CR32","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/S0092-8674(02)00716-X","volume":"109","author":"AK Bhunia","year":"2002","unstructured":"Bhunia AK, Piontek K, Boletta A, Liu L, Qian F, Xu PN, Germino FJ, Germino GG. PKD1 induces p21waf1 and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2. Cell. 2002;109(2):157\u201368.","journal-title":"Cell"},{"key":"6359_CR33","doi-asserted-by":"publisher","first-page":"338609","DOI":"10.1016\/j.aca.2021.338609","volume":"1168","author":"SZD Yan","year":"2021","unstructured":"Yan SZD, Wang C, Wang H, Guan X, Gao Y, Zhang X, Zhang N, Chen R. Characterization of RNA-binding proteins in the cell nucleus and cytoplasm. Anal Chim Acta. 2021;1168:338609.","journal-title":"Anal Chim Acta"},{"key":"6359_CR34","doi-asserted-by":"publisher","first-page":"109499","DOI":"10.1016\/j.cellsig.2019.109499","volume":"68","author":"B Roth\u00e9","year":"2020","unstructured":"Roth\u00e9 B, Gagnieux C, Leal-Esteban LC, Constam DB. Role of the RNA-binding protein Bicaudal-C1 and interacting factors in cystic kidney diseases. Cell Signal. 2020;68:109499.","journal-title":"Cell Signal"},{"key":"6359_CR35","doi-asserted-by":"publisher","first-page":"9570","DOI":"10.1074\/jbc.RA117.000975","volume":"293","author":"M Fragiadaki","year":"2018","unstructured":"Fragiadaki M, Zeidler MP. Ankyrin repeat and single KH domain 1 (ANKHD1) drives renal cancer cell proliferation via binding to and altering a subset of MiRNAs. J Biol Chem. 2018;293:9570\u20139.","journal-title":"J Biol Chem"},{"key":"6359_CR36","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1016\/j.omtn.2020.05.004","volume":"20","author":"C Yang","year":"2020","unstructured":"Yang C, Zheng J, Liu X, Xue Y, He Q, Dong Y, Wang D, Li Z, Liu L, Ma J, Cai H, Liu Y. Role of ANKHD1\/LINC00346\/ZNF655 feedback loop in regulating the glioma angiogenesis via Staufen1-Mediated mRNA decay. Mol Ther Nucleic Acids. 2020;20:866\u201378.","journal-title":"Mol Ther Nucleic Acids"},{"issue":"5","key":"6359_CR37","first-page":"1175","volume":"56","author":"XFHQ Liu","year":"2020","unstructured":"Liu XFHQ, Rong XZ, Yang M, Han YC, Yu JH, Lin XY. ANKHD1 promotes proliferation and invasion of non-small-cell lung cancer cells via regulating YAP oncoprotein expression and inactivating the Hippo pathway. Int J Oncol. 2020;56(5):1175\u201385.","journal-title":"Int J Oncol"},{"issue":"13","key":"6359_CR38","doi-asserted-by":"publisher","first-page":"jcs209551","DOI":"10.1242\/jcs.209551","volume":"131","author":"KH Fisher","year":"2018","unstructured":"Fisher KH, Fragiadaki M, Pugazhendhi D, Bausek N, Arredondo MA, Thomas SJ, Brown S, Zeidler MP. A genome-wide RNAi screen identifies MASK as a positive regulator of cytokine receptor stability. J Cell Sci. 2018;131(13):jcs209551.","journal-title":"J Cell Sci"},{"issue":"24","key":"6359_CR39","doi-asserted-by":"publisher","first-page":"4311","DOI":"10.1016\/j.febslet.2012.10.037","volume":"586","author":"A Dhyani","year":"2012","unstructured":"Dhyani A, Duarte AS, Machado-Neto JA, Favaro P, Ortega MM. Olalla Saad ST: ANKHD1 regulates cell cycle progression and proliferation in multiple myeloma cells. FEBS Lett. 2012;586(24):4311\u20138.","journal-title":"FEBS Lett"},{"issue":"3","key":"6359_CR40","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.kint.2016.10.039","volume":"91","author":"M Fragiadaki","year":"2017","unstructured":"Fragiadaki M, Lannoy M, Themanns M, Maurer B, Leonhard WN, Peters DJ, Moriggl R, Ong ACM. STAT5 drives abnormal proliferation in autosomal dominant polycystic kidney disease. Kidney Int. 2017;91(3):575\u201386.","journal-title":"Kidney Int"},{"issue":"9","key":"6359_CR41","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1038\/ng.2715","volume":"45","author":"M Ma","year":"2013","unstructured":"Ma M, Tian X, Igarashi P, Pazour GJ, Somlo S. Loss of cilia suppresses cyst growth in genetic models of autosomal dominant polycystic kidney disease. Nat Genet. 2013;45(9):1004\u201312.","journal-title":"Nat Genet"},{"issue":"8","key":"6359_CR42","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1038\/ng.3901","volume":"49","author":"TF Meehan","year":"2017","unstructured":"Meehan TF, Conte N, West DB, Jacobsen JO, Mason J, Warren J, Chen CK, Tudose I, Relac M, Matthews P, Karp N, Santos L, Fiegel T, Ring N, Westerberg H, Greenaway S, Sneddon D, Morgan H, Codner GF, Stewart ME, Brown J, Horner N, International Mouse Phenotyping Consortium, Haendel M, Washington N, Mungall CJ, Reynolds CL, Gallegos J, Gailus-Durner V, Sorg T, Pavlovic G, Bower LR, Moore M, Morse I, Gao X, Tocchini-Valentini GP, Obata Y, Cho SY, Seong JK, Seavitt J, Beaudet AL, Dickinson ME, Herault Y, Wurst W, de Angelis MH, Lloyd KCK, Flenniken AM, Nutter LMJ, Newbigging S, McKerlie C, Justice MJ, Murray SA, Svenson KL, Braun RE, White JK, Bradley A, Flicek P, Wells S, Skarnes WC, Adams DJ, Parkinson H, Mallon AM, Brown SDM, Smedley D. Disease model discovery from 3,328 gene knockouts by the international mouse phenotyping consortium. Nat Genet. 2017;49(8):1231\u20138.","journal-title":"Nat Genet"},{"issue":"2","key":"6359_CR43","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1038\/sj.ki.5002229","volume":"72","author":"E Parker","year":"2007","unstructured":"Parker E, Newby LJ, Sharpe CC, Rossetti S, Streets AJ, Harris PC, O\u2019Hare MJ, Ong ACM. Hyperproliferation of PKD1 cystic cells is induced by insulin-like growth factor-1 activation of the Ras\/Raf signalling system. Kidney Int. 2007;72(2):157\u201365.","journal-title":"Kidney Int"},{"issue":"2","key":"6359_CR44","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/j.kint.2020.02.012","volume":"98","author":"M Lannoy","year":"2020","unstructured":"Lannoy M, Valluru MK, Chang L, Abdela-Ali F, Peters DJM, Streets AJ, Ong ACM. The positive effect of selective prostaglandin E2 receptor EP2 and EP4 Blockade on cystogenesis in vitro is counteracted by increased kidney inflammation in vivo. Kidney Int. 2020;98(2):404\u201319.","journal-title":"Kidney Int"},{"issue":"2","key":"6359_CR45","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1080\/15384101.2019.1706903","volume":"19","author":"G Tchakarska","year":"2019","unstructured":"Tchakarska G, Sola B. The double dealing of Cyclin D1. Cell Cycle. 2019;19(2):163\u201378.","journal-title":"Cell Cycle"},{"issue":"12","key":"6359_CR46","doi-asserted-by":"publisher","first-page":"3357","DOI":"10.1038\/s41418-021-00823-x","volume":"28","author":"S Uxa","year":"2021","unstructured":"Uxa S, Castillo-Binder P, Kohler R, Stangner K, M\u00fcller GA, Engeland K. Ki-67 gene expression. Cell Death Differ. 2021;28(12):3357\u201370.","journal-title":"Cell Death Differ"},{"issue":"25","key":"6359_CR47","doi-asserted-by":"publisher","first-page":"9570","DOI":"10.1074\/jbc.RA117.000975","volume":"293","author":"M Fragiadaki","year":"2018","unstructured":"Fragiadaki M, Zeidler MP. Ankyrin repeat and single KH domain 1 (ANKHD1) drives renal cancer cell proliferation via binding to and altering a subset of MiRNAs. J Biol Chem. 2018;293(25):9570\u20139.","journal-title":"J Biol Chem"},{"key":"6359_CR48","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/bs.mcb.2019.05.008","volume":"153","author":"M Sharma","year":"2019","unstructured":"Sharma M, Reif GA, Wallace DP. In vitro cyst formation of ADPKD cells. Methods Cell Biol. 2019;153:93\u2013111.","journal-title":"Methods Cell Biol"},{"issue":"2","key":"6359_CR49","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1091\/mbc.8.2.287","volume":"8","author":"L Connell-Crowley","year":"1997","unstructured":"Connell-Crowley L, Harper JW, Goodrich DW. Cyclin D1\/Cdk4 regulates retinoblastoma protein-mediated cell cycle arrest by site-specific phosphorylation. Mol Biol Cell. 1997;8(2):287\u2013301.","journal-title":"Mol Biol Cell"},{"key":"6359_CR50","doi-asserted-by":"publisher","first-page":"41","DOI":"10.2147\/IJNRD.S125942","volume":"11","author":"L Sans-Atxer","year":"2018","unstructured":"Sans-Atxer L, Joly D. Tolvaptan in the treatment of autosomal dominant polycystic kidney disease: patient selection and special considerations. Int J Nephrol Renovasc Dis. 2018;11:41\u201351.","journal-title":"Int J Nephrol Renovasc Dis"},{"issue":"11","key":"6359_CR51","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1007\/s40264-015-0327-3","volume":"38","author":"PB Watkins","year":"2015","unstructured":"Watkins PB, Lewis JH, Kaplowitz N, Alpers DH, Blais JD, Smotzer DM, Krasa H, Ouyang J, Torres VE, Czerwiec FS, Zimmer CA. Clinical pattern of Tolvaptan-Associated liver injury in subjects with autosomal dominant polycystic kidney disease: analysis of clinical trials database. Drug Saf. 2015;38(11):1103\u201313.","journal-title":"Drug Saf"},{"issue":"1","key":"6359_CR52","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/s41392-020-0207-x","volume":"5","author":"B Hu","year":"2020","unstructured":"Hu B, Zhong L, Weng Y, Peng L, Huang Y, Zhao Y, Liang XJ. Therapeutic SiRNA: state of the Art. Signal Transduct Target Ther. 2020;5(1):101.","journal-title":"Signal Transduct Target Ther"},{"key":"6359_CR53","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/978-981-10-2041-4_3","volume":"933","author":"EJ Lee","year":"2016","unstructured":"Lee EJ. Cell proliferation and apoptosis in ADPKD. Adv Exp Med Biol. 2016;933:25\u201334.","journal-title":"Adv Exp Med Biol"},{"issue":"8","key":"6359_CR54","doi-asserted-by":"publisher","first-page":"413","DOI":"10.5483\/BMBRep.2020.53.8.087","volume":"53","author":"BO Almeida","year":"2020","unstructured":"Almeida BO, Machado-Neto JA. Emerging functions for ANKHD1 in cancer-related signaling pathways and cellular processes. BMB Rep. 2020;53(8):413\u20138.","journal-title":"BMB Rep"},{"issue":"16","key":"6359_CR55","doi-asserted-by":"publisher","first-page":"12834","DOI":"10.3390\/ijms241612834","volume":"24","author":"JL Mullenger","year":"2023","unstructured":"Mullenger JL, Zeidler MP, Fragiadaki M. Evaluating the molecular properties and function of ANKHD1, and its role in cancer. Int J Mol Sci. 2023;24(16):12834.","journal-title":"Int J Mol Sci"},{"key":"6359_CR56","doi-asserted-by":"crossref","unstructured":"DiRocco DP, Bisi J, Roberts P, Strum J, Wong KK, Sharpless N, et al. CDK4\/6 inhibition induces epithelial cell cycle arrest and ameliorates acute kidney injury. Am J Physiol-Renal Physiol. 2014;306(4):F379\u201388.","DOI":"10.1152\/ajprenal.00475.2013"},{"key":"6359_CR57","doi-asserted-by":"crossref","unstructured":"Osaki Y, Manolopoulou M, Ivanova AV, Vartanian N, Mignemi MP, Kern J, et al. Blocking cell cycle progression through CDK4\/6 protects against chronic kidney disease. JCI Insight. 2022;7(12):e158754.","DOI":"10.1172\/jci.insight.158754"},{"issue":"4","key":"6359_CR58","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1093\/ndt\/gfp611","volume":"25","author":"AK Ahrabi","year":"2009","unstructured":"Ahrabi AK, Jouret F, Marbaix E, Delporte C, Horie S, Mulroy S, Boulter C, Sandford R, Devuyst O. Glomerular and proximal tubule cysts as early manifestations of Pkd1 deletion. Nephrol Dial Transpl. 2009;25(4):1067\u201378.","journal-title":"Nephrol Dial Transpl"},{"issue":"2","key":"6359_CR59","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1128\/MCB.18.2.753","volume":"18","author":"AS Lundberg","year":"1998","unstructured":"Lundberg AS, Weinberg RA. Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct Cyclin-cdk complexes. Mol Cell Biol. 1998;18(2):753\u201361.","journal-title":"Mol Cell Biol"},{"key":"6359_CR60","doi-asserted-by":"publisher","first-page":"651541","DOI":"10.3389\/fonc.2021.651541","volume":"11","author":"B Wang","year":"2021","unstructured":"Wang B, Li R, Wu S, Liu X, Ren J, Li J, Bi K, Wang Y, Jia H. Breast cancer resistance to Cyclin-Dependent kinases 4\/6 inhibitors: intricacy of the molecular mechanisms. Front Oncol. 2021;11:651541.","journal-title":"Front Oncol"},{"issue":"7","key":"6359_CR61","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1038\/cdd.2011.202","volume":"19","author":"F Rizzolio","year":"2012","unstructured":"Rizzolio F, Lucchetti C, Caligiuri I, Marchesi I, Caputo M, Klein-Szanto AJ, Bagella L, Castronovo M, Giordano A. Retinoblastoma tumor-suppressor protein phosphorylation and inactivation depend on direct interaction with Pin1. Cell Death Differ. 2012;19(7):1152\u201361.","journal-title":"Cell Death Differ"},{"issue":"1","key":"6359_CR62","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.kint.2021.03.024","volume":"100","author":"K Lee","year":"2021","unstructured":"Lee K, Gusella GL, He JC. Epithelial proliferation and cell cycle dysregulation in kidney injury and disease. Kidney Int. 2021;100(1):67\u201378.","journal-title":"Kidney Int"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-025-06359-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-025-06359-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-025-06359-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T11:09:56Z","timestamp":1781608196000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12967-025-06359-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,2]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["6359"],"URL":"https:\/\/doi.org\/10.1186\/s12967-025-06359-9","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,2]]},"assertion":[{"value":"3 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 March 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 June 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"N\/A.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"N\/A.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"None.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"612"}}