{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T14:24:10Z","timestamp":1789914250618,"version":"4.0.1"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T00:00:00Z","timestamp":1539129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Microcephalin\u20101 (MCPH1) exists as 2 isoforms that regulate cyclin\u2010dependent kinase\u20101 activation and chromosome condensation during mitosis, with MCPH1 mutations causing primary microcephaly. MCPH1 is also a tumor suppressor protein, with roles in DNA damage repair\/checkpoints. Despite these important roles, there is little information on the cellular regulation of MCPH1. We show that both MCPH1 isoforms are phosphorylated in a cyclin\u2010dependent kinase\u20101\u2013dependent manner in mitosis and identify several novel phosphorylation sites. Upon mitotic exit, MCPH1 isoforms were degraded by the anaphase\u2010promoting complex\/cyclosome\u2013CDH1 E3 ligase complex. Anaphase\u2010promoting complex\/cyclosome\u2013CDH1 target proteins generally have D\u2010Box or KEN\u2010Box degron sequences. We found that MCPH1 isoforms are degraded independently, with the long isoform degradation being D\u2010Box dependent, whereas the short isoform was KEN\u2010Box dependent. Our research identifies several novel mechanisms regulating MCPH1 and also highlights important issues with several commercial MCPH1 antibodies, with potential relevance to previously published data.\u2014Meyer, S. K., Dunn, M., Vidler, D. S., Porter, A., Blain, P. G., Jowsey, P. A. Phosphorylation of MCPH1 isoforms during mitosis followed by isoform\u2010specific degradation by APC\/C\u2010CDH1. FASEB J. 33, 2796\u20132808 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201801353r","type":"journal-article","created":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T14:13:12Z","timestamp":1539180792000},"page":"2796-2808","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Phosphorylation of MCPH1 isoforms during mitosis followed by isoform\u2010specific degradation by APC\/C\u2010CDH1"],"prefix":"10.1096","volume":"33","author":[{"given":"Stephanie K.","family":"Meyer","sequence":"first","affiliation":[{"name":"National Intitute for Health Research (NIHR) Health Protection Research Unit for Chemical and Radiation Threats and Hazards Institute of Cellular Medicine Newcastle University Newcastle upon Tyne United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Dunn","sequence":"additional","affiliation":[{"name":"National Intitute for Health Research (NIHR) Health Protection Research Unit for Chemical and Radiation Threats and Hazards Institute of Cellular Medicine Newcastle University Newcastle upon Tyne United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S.","family":"Vidier","sequence":"additional","affiliation":[{"name":"National Intitute for Health Research (NIHR) Health Protection Research Unit for Chemical and Radiation Threats and Hazards Institute of Cellular Medicine Newcastle University Newcastle upon Tyne United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Porter","sequence":"additional","affiliation":[{"name":"Newcastle University Protein and Proteome Analysis Newcastle University Newcastle upon Tyne United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter G.","family":"Blain","sequence":"additional","affiliation":[{"name":"National Intitute for Health Research (NIHR) Health Protection Research Unit for Chemical and Radiation Threats and Hazards Institute of Cellular Medicine Newcastle University Newcastle upon Tyne United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Jowsey","sequence":"additional","affiliation":[{"name":"National Intitute for Health Research (NIHR) Health Protection Research Unit for Chemical and Radiation Threats and Hazards Institute of Cellular Medicine Newcastle University Newcastle upon Tyne United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1086\/341283"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmw048"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1431"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200810159"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1086\/422855"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.5.3.2412"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M804080200"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201106141"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-12793-7"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2342"},{"key":"e_1_2_8_12_1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s00384-016-2675-6","article-title":"Candidate tumor suppressor gene MCPH1 is mutated in colorectal and gastric cancers","volume":"32","author":"Jo Y. 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