{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:51:43Z","timestamp":1791352303725,"version":"4.3.1"},"reference-count":77,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100020884","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["Fondecyt 1260446"],"award-info":[{"award-number":["Fondecyt 1260446"]}],"id":[{"id":"10.13039\/501100020884","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020884","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["Fondap 15150012"],"award-info":[{"award-number":["Fondap 15150012"]}],"id":[{"id":"10.13039\/501100020884","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020884","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["ICN2021_044"],"award-info":[{"award-number":["ICN2021_044"]}],"id":[{"id":"10.13039\/501100020884","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020884","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["Fondecyt 1231105"],"award-info":[{"award-number":["Fondecyt 1231105"]}],"id":[{"id":"10.13039\/501100020884","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    P53\u2010related protein kinase (PRPK; TP53RK) is an evolutionarily conserved atypical kinase whose biology reveals an unexpected integration of translational control, cytoskeletal regulation, and cell\u2010type\u2010specific stress responses. As a core component of the TCTC complex (\n                    <jats:styled-content>T<\/jats:styled-content>\n                    hreonyl\u2010\n                    <jats:styled-content>C<\/jats:styled-content>\n                    arbamoyl\n                    <jats:styled-content>T<\/jats:styled-content>\n                    ransferase\n                    <jats:styled-content>C<\/jats:styled-content>\n                    omplex), PRPK participates in the universally conserved synthesis of the tRNA modification t\n                    <jats:sup>6<\/jats:sup>\n                    A, an essential process for translational fidelity, proteostasis, and cellular viability. Structural and biochemical studies from yeast to humans highlight a deeply conserved ATPase\u2010driven mechanism in which PRPK undergoes conformational rearrangements to activate the catalytic subunit Tcs3, thereby coordinating tRNA positioning. Beyond this canonical role, PRPK displays additional functions. In\n                    <jats:italic>Drosophila<\/jats:italic>\n                    and mammalian systems, PRPK engages cytoskeletal regulators, including Rab35 and Arp2\/3 subunits, to influence actin organization, neuronal polarity, and cell migration. These interactions suggest a second, TCTC\u2010independent functional module through which PRPK integrates signaling pathways such as AKT and TOPK to shape cell survival, axon specification, and tumor progression. Dysregulation of PRPK in human disease further underscores its pleiotropy, as gain\u2010of\u2010function mechanisms promote oncogenesis and metastasis. In contrast, loss\u2010of\u2010function mutations in PRPK or other TCTC components cause Galloway\u2013Mowat syndrome, characterized by microcephaly, nephrotic syndrome, and profound defects in proteostasis and cytoskeletal integrity. This Perspective synthesizes emerging concepts of PRPK as a dual\u2010role regulator, acting in tRNA biology as well as in cytoskeletal and stress responses. We delineate unresolved questions regarding substrate identity, structural regulation, cell\u2010type specificity, and the feasibility of selectively targeting PRPK for therapeutic purposes. Taken together, these findings reveal the richness and complexity of PRPK functions as a molecular regulator of translation, signaling, and cytoskeletal dynamics that are evolutionarily and mechanistically intertwined.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70562-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70562","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:48:26Z","timestamp":1791352106000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual Roles of p53\u2010Related Protein Kinase in Cytoskeletal Remodeling and Translational Control"],"prefix":"10.1111","volume":"170","author":[{"given":"Emiliano","family":"Molina","sequence":"first","affiliation":[{"name":"Department of Biology, Faculty of Sciences Universidad de Chile  Santiago Chile"},{"name":"Millennium Institute Center for Genome Regulation  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4250-7216","authenticated-orcid":false,"given":"David","family":"Villarroel\u2010Campos","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases and UCL Queen Square Motor Neuron Disease Centre, UCL Queen Square Institute of Neurology University College London  London UK"},{"name":"UK Dementia Research Institute University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Sciences Universidad de Chile  Santiago Chile"},{"name":"Geroscience Center for Brain Health and Metabolism (GERO)  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"Glavic","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Sciences Universidad de Chile  Santiago Chile"},{"name":"Millennium Institute Center for Genome Regulation  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0335-1482","authenticated-orcid":false,"given":"Christian","family":"Gonzalez\u2010Billault","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Sciences Universidad de Chile  Santiago Chile"},{"name":"Geroscience Center for Brain Health and Metabolism (GERO)  Santiago Chile"},{"name":"Department of Neuroscience, Faculty of Medicine Universidad de Chile  Santiago Chile"},{"name":"The Buck Institute for Research on Aging  Novato California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"44003","DOI":"10.1074\/jbc.M105669200","article-title":"Cloning and Characterization of a p53\u2010Related Protein Kinase Expressed in Interleukin\u20102\u2010Activated Cytotoxic T\u2010Cells, Epithelial Tumor Cell Lines, and the Testes","volume":"276","author":"Abe Y.","year":"2001","journal-title":"Journal of Biological Chemistry"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.bbrc.2006.03.071","article-title":"A Small Ras\u2010Like Protein Ray\/Rab1c Modulates the p53\u2010Regulating Activity of PRPK","volume":"344","author":"Abe Y.","year":"2006","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-019-11951-x","article-title":"Defects in t 6 A tRNA Modification due to GON7 and YRDC Mutations Lead to Galloway\u2010Mowat Syndrome","volume":"10","author":"Arrondel C.","year":"2019","journal-title":"Nature Communications"},{"key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"3465","DOI":"10.1038\/s41467-018-05958-z","article-title":"LRRK2 Kinase Regulates \u03b1\u2010Synuclein Propagation via RAB35 Phosphorylation","volume":"9","author":"Bae E.\u2010J.","year":"2018","journal-title":"Nature Communications"},{"key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"6233","DOI":"10.1038\/s41467-020-19990-5","article-title":"A Substrate Binding Model for the KEOPS tRNA Modifying Complex","volume":"11","author":"Beenstock J.","year":"2020","journal-title":"Nature Communications"},{"key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1038\/ng.3933","article-title":"Mutations in KEOPS\u2010Complex Genes Cause Nephrotic Syndrome With Primary Microcephaly","volume":"49","author":"Braun D. A.","year":"2017","journal-title":"Nature Genetics"},{"key":"e_1_2_11_8_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/msb.2010.52","article-title":"Kinase\/Phosphatase Overexpression Reveals Pathways Regulating Hippocampal Neuron Morphology","volume":"6","author":"Buchser W.","year":"2010","journal-title":"Molecular Systems Biology"},{"key":"e_1_2_11_9_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fnmol.2023.1116949","article-title":"Novel TP53RK Variants Cause Varied Clinical Features of Galloway\u2013Mowat Syndrome Without Nephrotic Syndrome in Three Unrelated Chinese Patients","volume":"16","author":"Chen J.","year":"2023","journal-title":"Frontiers in Molecular Neuroscience"},{"key":"e_1_2_11_10_1","doi-asserted-by":"crossref","DOI":"10.1128\/mbio.02944-22","article-title":"Unraveling the Pathobiological Role of the Fungal KEOPS Complex in \n                     Cryptococcus neoformans","volume":"13","author":"Choi Y.","year":"2022","journal-title":"mBio"},{"key":"e_1_2_11_11_1","doi-asserted-by":"crossref","first-page":"36122","DOI":"10.1038\/s41598-025-21082-7","article-title":"Identifying TP53RK as a Key Regulator of Colorectal Cancer Survival and a Potential Therapeutic Target","volume":"15","author":"Choi Y.","year":"2025","journal-title":"Scientific Reports"},{"key":"e_1_2_11_12_1","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1002\/(SICI)1097-0061(19970315)13:3<287::AID-YEA75>3.0.CO;2-5","article-title":"Analysis of an 11\u00b76 Kb Region From the Right Arm of Chromosome VII of \n                     Saccharomyces cerevisiae\n                   Between the RAD2 and the MES1 Genes Reveals the Presence of Three New Genes","volume":"13","author":"Clemente M. L.","year":"1997","journal-title":"Yeast"},{"key":"e_1_2_11_13_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0042822","article-title":"The Human EKC\/KEOPS Complex Is Recruited to Cullin2 Ubiquitin Ligases by the Human Tumour Antigen PRAME","volume":"7","author":"Costessi A.","year":"2012","journal-title":"PLoS One"},{"key":"e_1_2_11_14_1","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.cell.2005.06.044","article-title":"Higher\u2010Order Substrate Recognition of eIF2\u03b1 by the RNA\u2010Dependent Protein Kinase PKR","volume":"122","author":"Dar A. C.","year":"2005","journal-title":"Cell"},{"key":"e_1_2_11_15_1","doi-asserted-by":"crossref","first-page":"6148","DOI":"10.1093\/nar\/gkr178","article-title":"Gcn4 Misregulation Reveals a Direct Role for the Evolutionary Conserved EKC\/KEOPS in the t6A Modification of tRNAs","volume":"39","author":"Daugeron M.\u2010C.","year":"2011","journal-title":"Nucleic Acids Research"},{"key":"e_1_2_11_16_1","doi-asserted-by":"crossref","first-page":"13666","DOI":"10.1074\/jbc.M112.344028","article-title":"Biosynthesis of Threonylcarbamoyl Adenosine (t6A), a Universal tRNA Nucleoside","volume":"287","author":"Deutsch C.","year":"2012","journal-title":"Journal of Biological Chemistry"},{"key":"e_1_2_11_17_1","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/j.cell.2005.12.044","article-title":"A Genome\u2010Wide Screen Identifies the Evolutionarily Conserved KEOPS Complex as a Telomere Regulator","volume":"124","author":"Downey M.","year":"2006","journal-title":"Cell"},{"key":"e_1_2_11_18_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1005625","article-title":"Identifying Direct Contacts Between Protein Complex Subunits From Their Conditional Dependence in Proteomics Datasets","volume":"13","author":"Drew K.","year":"2017","journal-title":"PLoS Computational Biology"},{"key":"e_1_2_11_19_1","doi-asserted-by":"crossref","first-page":"2894","DOI":"10.1093\/nar\/gkp152","article-title":"The Universal YrdC\/Sua5 Family Is Required for the Formation of Threonylcarbamoyladenosine in tRNA","volume":"37","author":"El Yacoubi B.","year":"2009","journal-title":"Nucleic Acids Research"},{"key":"e_1_2_11_20_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S0014-5793(03)00770-1","article-title":"Functional Homology Between Yeast piD261\/Bud32 and Human PRPK: Both Phosphorylate p53 and PRPK Partially Complements piD261\/Bud32 Deficiency","volume":"549","author":"Facchin S.","year":"2003","journal-title":"FEBS Letters"},{"key":"e_1_2_11_21_1","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1042\/bj20011376","article-title":"Structure\u2010Function Analysis of Yeast piD261\/Bud32, an Atypical Protein Kinase Essential for Normal Cell Life","volume":"364","author":"Facchin S.","year":"2002","journal-title":"Biochemical Journal"},{"key":"e_1_2_11_22_1","doi-asserted-by":"crossref","first-page":"2680","DOI":"10.1007\/s00018-007-7179-7","article-title":"Phosphorylation and Activation of the Atypical Kinase p53\u2010Related Protein Kinase (PRPK) by Akt\/PKB","volume":"64","author":"Facchin S.","year":"2007","journal-title":"Cellular and Molecular Life Sciences: CMLS"},{"key":"e_1_2_11_23_1","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1016\/S0006-291X(02)02090-9","article-title":"Acidophilic Character of Yeast PID261\/BUD32, a Putative Ancestor of Eukaryotic Protein Kinases","volume":"296","author":"Facchin S.","year":"2002","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"e_1_2_11_24_1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1136\/jmg.5.4.319","article-title":"Congenital Microcephaly With Hiatus Hernia and Nephrotic Syndrome in Two Sibs","volume":"5","author":"Galloway W. H.","year":"1968","journal-title":"Journal of Medical Genetics"},{"key":"e_1_2_11_25_1","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1158\/1541-7786.MCR-19-0144","article-title":"Identification of TP53RK\u2010Binding Protein (TPRKB) Dependency in TP53\u2010Deficient Cancers","volume":"17","author":"Goswami M. T.","year":"2019","journal-title":"Molecular Cancer Research"},{"key":"e_1_2_11_26_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0076622","article-title":"Screening E3 Substrates Using a Live Phage Display Library","volume":"8","author":"Guo Z.","year":"2013","journal-title":"PLoS One"},{"key":"e_1_2_11_27_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jmb.2025.169106","article-title":"Structural Snapshots of Human tRNA Modifying Enzymes","volume":"437","author":"Hammermeister A.","year":"2025","journal-title":"Journal of Molecular Biology"},{"key":"e_1_2_11_28_1","doi-asserted-by":"crossref","first-page":"5684","DOI":"10.1093\/nar\/gkz228","article-title":"KEOPS Complex Promotes Homologous Recombination via DNA Resection","volume":"47","author":"He M.\u2010H.","year":"2019","journal-title":"Nucleic Acids Research"},{"key":"e_1_2_11_29_1","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1038\/emboj.2008.157","article-title":"Structure of the Archaeal Kae1\/Bud32 Fusion Protein MJ1130: A Model for the Eukaryotic EKC\/KEOPS Subcomplex","volume":"27","author":"Hecker A.","year":"2008","journal-title":"EMBO Journal"},{"key":"e_1_2_11_30_1","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1182\/blood-2016-09-738500","article-title":"p53\u2010Related Protein Kinase Confers Poor Prognosis and Represents a Novel Therapeutic Target in Multiple Myeloma","volume":"129","author":"Hideshima T.","year":"2017","journal-title":"Blood"},{"key":"e_1_2_11_31_1","doi-asserted-by":"crossref","DOI":"10.3389\/fped.2024.1360867","article-title":"Case Report: Novel Compound Heterozygous TPRKB Variants Cause Galloway\u2010Mowat Syndrome","volume":"12","author":"Hiraide T.","year":"2024","journal-title":"Frontiers in Pediatrics"},{"key":"e_1_2_11_32_1","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1186\/s12964-025-02307-8","article-title":"Genetics and Phenotypic Heterogeneity of Galloway\u2010Mowat Syndrome","volume":"23","author":"Huang L.","year":"2025","journal-title":"Cell Communication and Signaling: CCS"},{"key":"e_1_2_11_33_1","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1186\/s12881-018-0649-y","article-title":"A Familial Case of Galloway\u2010Mowat Syndrome due to a Novel TP53RK Mutation: A Case Report","volume":"19","author":"Hyun H. S.","year":"2018","journal-title":"BMC Medical Genetics"},{"key":"e_1_2_11_34_1","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1242\/dev.086918","article-title":"Drosophila p53\u2010Related Protein Kinase Is Required for PI3K\/TOR Pathway\u2010Dependent Growth","volume":"140","author":"Ibar C.","year":"2013","journal-title":"Development (Cambridge, England)"},{"key":"e_1_2_11_35_1","doi-asserted-by":"crossref","DOI":"10.1128\/spectrum.02866-22","article-title":"Unraveling Capsule Biosynthesis and Signaling Networks in \n                     Cryptococcus neoformans","volume":"10","author":"Jang E.\u2010H.","year":"2022","journal-title":"Microbiology Spectrum"},{"key":"e_1_2_11_36_1","doi-asserted-by":"crossref","first-page":"3576","DOI":"10.1038\/sj.emboj.7601235","article-title":"Yeast Homolog of a Cancer\u2010Testis Antigen Defines a New Transcription Complex","volume":"25","author":"Kisseleva\u2010Romanova E.","year":"2006","journal-title":"EMBO Journal"},{"key":"e_1_2_11_37_1","doi-asserted-by":"crossref","DOI":"10.1242\/jcs.261003","article-title":"Phosphorylation of Rab29 at Ser185 Regulates Its Localization and Role in the Lysosomal Stress Response in Concert With LRRK2","volume":"136","author":"Komori T.","year":"2023","journal-title":"Journal of Cell Science"},{"key":"e_1_2_11_38_1","doi-asserted-by":"crossref","first-page":"8950","DOI":"10.1021\/bi301233d","article-title":"Mechanism of N6\u2010Threonylcarbamoyladenonsine (t6A) Biosynthesis: Isolation and Characterization of the Intermediate Threonylcarbamoyl\u2010AMP","volume":"51","author":"Lauhon C. T.","year":"2012","journal-title":"Biochemistry"},{"key":"e_1_2_11_39_1","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1101\/gr.8.10.1038","article-title":"Novel Families of Putative Protein Kinases in Bacteria and Archaea: Evolution of the \u201cEukaryotic\u201d Protein Kinase Superfamily","volume":"8","author":"Leonard C. J.","year":"1998","journal-title":"Genome Research"},{"key":"e_1_2_11_40_1","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/s42003-021-01683-4","article-title":"Crystal Structure of the Human PRPK\u2010TPRKB Complex","volume":"4","author":"Li J.","year":"2021","journal-title":"Communications Biology"},{"key":"e_1_2_11_41_1","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1261\/rna.053934.115","article-title":"An Extensive Allelic Series of Drosophila kae1 Mutants Reveals Diverse and Tissue\u2010Specific Requirements for t6A Biogenesis","volume":"21","author":"Lin C.\u2010J.","year":"2015","journal-title":"RNA"},{"key":"e_1_2_11_42_1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jgg.2018.03.004","article-title":"Yeast KEOPS Complex Regulates Telomere Length Independently of Its t6A Modification Function","volume":"45","author":"Liu Y.\u2010Y.","year":"2018","journal-title":"Journal of Genetics and Genomics"},{"key":"e_1_2_11_43_1","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1038\/leu.2012.119","article-title":"Cereblon Is a Direct Protein Target for Immunomodulatory and Antiproliferative Activities of Lenalidomide and Pomalidomide","volume":"26","author":"Lopez\u2010Girona A.","year":"2012","journal-title":"Leukemia"},{"key":"e_1_2_11_44_1","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1042\/bj20030638","article-title":"Analysis of the Interaction Between piD261\/Bud32, an Evolutionarily Conserved Protein Kinase of Saccharomyces Cerevisiae, and the Grx4 Glutaredoxin","volume":"377","author":"Lopreiato R.","year":"2004","journal-title":"Biochemical Journal"},{"key":"e_1_2_11_45_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2025.1624237","article-title":"The Kinase Bud32 Regulates Iron Homeostasis in Fungal Pathogen \n                     Cryptococcus neoformans","volume":"16","author":"Ma Y.","year":"2025","journal-title":"Frontiers in Immunology"},{"key":"e_1_2_11_46_1","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/s42003-023-04826-x","article-title":"RAB35 Is Required for Murine Hippocampal Development and Functions by Regulating Neuronal Cell Distribution","volume":"6","author":"Maejima I.","year":"2023","journal-title":"Communications Biology"},{"key":"e_1_2_11_47_1","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.4103\/NRR.NRR-D-23-01543","article-title":"New Aspects of a Small GTPase RAB35 in Brain Development and Function","volume":"20","author":"Maejima I.","year":"2025","journal-title":"Neural Regeneration Research"},{"key":"e_1_2_11_48_1","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1126\/science.1075762","article-title":"The Protein Kinase Complement of the Human Genome","volume":"298","author":"Manning G.","year":"2002","journal-title":"Science"},{"key":"e_1_2_11_49_1","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.molcel.2008.10.002","article-title":"Atomic Structure of the KEOPS Complex: An Ancient Protein Kinase\u2010Containing Molecular Machine","volume":"32","author":"Mao D. Y. L.","year":"2008","journal-title":"Molecular Cell"},{"key":"e_1_2_11_50_1","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1038\/emboj.2009.92","article-title":"Sua5p a Single\u2010Stranded Telomeric DNA\u2010Binding Protein Facilitates Telomere Replication","volume":"28","author":"Meng F.\u2010L.","year":"2009","journal-title":"EMBO Journal"},{"key":"e_1_2_11_51_1","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/S0006-291X(03)00333-4","article-title":"Identification of CGI\u2010121, a Novel PRPK (p53\u2010Related Protein Kinase)\u2010Binding Protein","volume":"303","author":"Miyoshi A.","year":"2003","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"e_1_2_11_52_1","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2022.859105","article-title":"p53 Related Protein Kinase Is Required for Arp2\/3\u2010Dependent Actin Dynamics of Hemocytes in \n                     Drosophila melanogaster","volume":"10","author":"Molina E.","year":"2022","journal-title":"Frontiers in Cell and Development Biology"},{"key":"e_1_2_11_53_1","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1038\/nsmb861","article-title":"The Role of Modifications in Codon Discrimination by tRNA Lys UUU","volume":"11","author":"Murphy F. V.","year":"2004","journal-title":"Nature Structural & Molecular Biology"},{"key":"e_1_2_11_54_1","doi-asserted-by":"crossref","first-page":"10633","DOI":"10.1038\/s41467-024-54787-w","article-title":"Structures of KEOPS Bound to tRNA Reveal Functional Roles of the Kinase Bud32","volume":"15","author":"Ona Chuquimarca S. M.","year":"2024","journal-title":"Nature Communications"},{"key":"e_1_2_11_55_1","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1080\/21541248.2016.1277840","article-title":"Rabs Set the Stage for Polarity","volume":"9","author":"Parker S. S.","year":"2018","journal-title":"Small GTPases"},{"key":"e_1_2_11_56_1","doi-asserted-by":"crossref","first-page":"5919","DOI":"10.1111\/j.1742-4658.2008.06721.x","article-title":"Phosphorylation of the \n                     Saccharomyces cerevisiae\n                   Grx4p Glutaredoxin by the Bud32p Kinase Unveils a Novel Signaling Pathway Involving Sch9p, a Yeast Member of the Akt \/ PKB Subfamily","volume":"275","author":"Peggion C.","year":"2008","journal-title":"FEBS Journal"},{"key":"e_1_2_11_57_1","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1093\/nar\/gks1287","article-title":"In Vitro Biosynthesis of a Universal t6A tRNA Modification in Archaea and Eukarya","volume":"41","author":"Perrochia L.","year":"2013","journal-title":"Nucleic Acids Research"},{"key":"e_1_2_11_58_1","doi-asserted-by":"crossref","first-page":"9484","DOI":"10.1093\/nar\/gkt720","article-title":"Functional Assignment of KEOPS\/EKC Complex Subunits in the Biosynthesis of the Universal t6A tRNA Modification","volume":"41","author":"Perrochia L.","year":"2013","journal-title":"Nucleic Acids Research"},{"key":"e_1_2_11_59_1","doi-asserted-by":"crossref","first-page":"5633","DOI":"10.1038\/s41388-018-0350-9","article-title":"Targeting PRPK and TOPK for Skin Cancer Prevention and Therapy","volume":"37","author":"Roh E.","year":"2018","journal-title":"Oncogene"},{"key":"e_1_2_11_60_1","first-page":"25","article-title":"Modulation of the Proteostasis Machinery to Overcome Stress Caused by Diminished Levels of t(6)A\u2010Modified tRNAs in Drosophila","volume":"7","author":"Rojas\u2010Benitez D.","year":"2017","journal-title":"Biomolecules"},{"key":"e_1_2_11_61_1","doi-asserted-by":"crossref","first-page":"168","DOI":"10.4161\/fly.25227","article-title":"The Drosophila EKC\/KEOPS Complex: Roles in Protein Synthesis Homeostasis and Animal Growth","volume":"7","author":"Rojas\u2010Benitez D.","year":"2013","journal-title":"Fly (Austin)"},{"key":"e_1_2_11_62_1","doi-asserted-by":"crossref","first-page":"18699","DOI":"10.1074\/jbc.M115.665406","article-title":"The Levels of a Universally Conserved tRNA Modification Regulate Cell Growth","volume":"290","author":"Rojas\u2010Benitez D.","year":"2015","journal-title":"Journal of Biological Chemistry"},{"key":"e_1_2_11_63_1","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1038\/emboj.2010.343","article-title":"The Highly Conserved KEOPS\/EKC Complex Is Essential for a Universal tRNA Modification, t6A: Proteins Essential for a tRNA Modification, t6A","volume":"30","author":"Srinivasan M.","year":"2011","journal-title":"EMBO Journal"},{"key":"e_1_2_11_64_1","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0014-5793(97)00980-0","article-title":"Biochemical Evidence That \n                     Saccharomyces cerevisiae\n                   YGR262c Gene, Required for Normal Growth, Encodes a Novel Ser\/Thr\u2010Specific Protein Kinase","volume":"414","author":"Stocchetto S.","year":"1997","journal-title":"FEBS Letters"},{"key":"e_1_2_11_65_1","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.4161\/15476286.2014.992277","article-title":"Diversity of the Biosynthesis Pathway for Threonylcarbamoyladenosine (t6A), a Universal Modification of tRNA","volume":"11","author":"Thiaville P. C.","year":"2014","journal-title":"RNA Biology"},{"key":"e_1_2_11_66_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.15698\/mic2016.01.473","article-title":"Global Translational Impacts of the Loss of the tRNA Modification t(6)A in Yeast","volume":"3","author":"Thiaville P. C.","year":"2016","journal-title":"Microbial Cell"},{"key":"e_1_2_11_67_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.gep.2021.119215","article-title":"Galloway\u2010Mowat Syndrome: New Insights From Bioinformatics and Expression During Xenopus Embryogenesis","volume":"42","author":"Treimer E.","year":"2021","journal-title":"Gene Expression Patterns"},{"key":"e_1_2_11_68_1","doi-asserted-by":"crossref","DOI":"10.1126\/science.1260419","article-title":"Proteomics. Tissue\u2010Based Map of the Human Proteome","volume":"347","author":"Uhl\u00e9n M.","year":"2015","journal-title":"Science"},{"key":"e_1_2_11_69_1","doi-asserted-by":"crossref","first-page":"7298","DOI":"10.1523\/JNEUROSCI.4064-15.2016","article-title":"Rab35 Functions in Axon Elongation Are Regulated by P53\u2010Related Protein Kinase in a Mechanism That Involves Rab35 Protein Degradation and the Microtubule\u2010Associated Protein 1B","volume":"36","author":"Villarroel\u2010Campos D.","year":"2016","journal-title":"Journal of Neuroscience"},{"key":"e_1_2_11_70_1","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1093\/nar\/gkw1181","article-title":"Proteomic Analysis of the Human KEOPS Complex Identifies C14ORF142 as a Core Subunit Homologous to Yeast Gon7","volume":"45","author":"Wan L. C. K.","year":"2017","journal-title":"Nucleic Acids Research"},{"key":"e_1_2_11_71_1","doi-asserted-by":"crossref","first-page":"6332","DOI":"10.1093\/nar\/gkt322","article-title":"Reconstitution and Characterization of Eukaryotic N6\u2010Threonylcarbamoylation of tRNA Using a Minimal Enzyme System","volume":"41","author":"Wan L. C. K.","year":"2013","journal-title":"Nucleic Acids Research"},{"key":"e_1_2_11_72_1","doi-asserted-by":"crossref","first-page":"6971","DOI":"10.1093\/nar\/gkw542","article-title":"Structural and Functional Characterization of KEOPS Dimerization by Pcc1 and Its Role in t6A Biosynthesis","volume":"44","author":"Wan L. C. K.","year":"2016","journal-title":"Nucleic Acids Research"},{"key":"e_1_2_11_73_1","doi-asserted-by":"crossref","DOI":"10.1002\/advs.202301753","article-title":"TP53RK Drives the Progression of Chronic Kidney Disease by Phosphorylating Birc5","volume":"10","author":"Wu M.","year":"2023","journal-title":"Advanced Science"},{"key":"e_1_2_11_74_1","doi-asserted-by":"crossref","first-page":"4211","DOI":"10.1074\/jbc.M115.669978","article-title":"A Novel Naphthalimide Compound Restores p53 Function in Non\u2010Small Cell Lung Cancer by Reorganizing the Bak Center Dot Bcl\u2010Xl Complex and Triggering Transcriptional Regulation","volume":"291","author":"Zhang G.","year":"2016","journal-title":"Journal of Biological Chemistry"},{"key":"e_1_2_11_75_1","doi-asserted-by":"crossref","first-page":"3358","DOI":"10.1093\/nar\/gkv155","article-title":"Crystal Structures of the Gon7\/Pcc1 and Bud32\/Cgi121 Complexes Provide a Model for the Complete Yeast KEOPS Complex","volume":"43","author":"Zhang W.","year":"2015","journal-title":"Nucleic Acids Research"},{"key":"e_1_2_11_76_1","doi-asserted-by":"crossref","first-page":"4523","DOI":"10.1093\/nar\/gkae179","article-title":"Molecular Basis of \n                     A. thaliana\n                   KEOPS Complex in Biosynthesizing tRNA t6A","volume":"52","author":"Zheng X.","year":"2024","journal-title":"Nucleic Acids Research"},{"key":"e_1_2_11_77_1","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1158\/1535-7163.MCT-17-0628","article-title":"Targeting PRPK Function Blocks Colon Cancer Metastasis","volume":"17","author":"Zykova T.","year":"2018","journal-title":"Molecular Cancer Therapeutics"},{"key":"e_1_2_11_78_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.ebiom.2017.04.003","article-title":"The T\u2010LAK Cell\u2010Originated Protein Kinase Signal Pathway Promotes Colorectal Cancer Metastasis","volume":"18","author":"Zykova T. A.","year":"2017","journal-title":"eBioMedicine"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.70562","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jnc.70562","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.70562","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:48:35Z","timestamp":1791352115000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.70562"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":77,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1111\/jnc.70562"],"URL":"https:\/\/doi.org\/10.1111\/jnc.70562","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-05-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70562"}}