{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T15:02:34Z","timestamp":1774623754946,"version":"3.50.1"},"reference-count":83,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T00:00:00Z","timestamp":1603324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001505","name":"Health Research Council of New Zealand","doi-asserted-by":"publisher","award":["18-150"],"award-info":[{"award-number":["18-150"]}],"id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Post-translational modification of histone proteins plays a major role in histone\u2013DNA packaging and ultimately gene expression. Attachment of ubiquitin to the C-terminal tail of histone H2A (H2AK119Ub in mammals) is particularly relevant to the repression of gene transcription, and is removed by the Polycomb Repressive-Deubiquitinase (PR-DUB) complex. Here, we outline recent advances in the understanding of PR-DUB regulation, which have come through structural studies of the Drosophila melanogaster PR-DUB, biochemical investigation of the human PR-DUB, and functional studies of proteins that associate with the PR-DUB. In humans, mutations in components of the PR-DUB frequently give rise to malignant mesothelioma, melanomas, and renal cell carcinoma, and increase disease risk from carcinogens. Diverse mechanisms may underlie disruption of the PR-DUB across this spectrum of disease. Comparing and contrasting the PR-DUB in mammals and Drosophila reiterates the importance of H2AK119Ub through evolution, provides clues as to how the PR-DUB is dysregulated in disease, and may enable new treatment approaches in cancers where the PR-DUB is disrupted.<\/jats:p>","DOI":"10.3390\/ijms21217837","type":"journal-article","created":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T10:27:58Z","timestamp":1603362478000},"page":"7837","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Molecular Regulation of the Polycomb Repressive-Deubiquitinase"],"prefix":"10.3390","volume":"21","author":[{"given":"Cameron J.","family":"Reddington","sequence":"first","affiliation":[{"name":"Department of Biochemistry, School of Biomedical Sciences, University of Otago, P.O. Box 56, 710 Cumberland St., Dunedin 9054, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3192-6984","authenticated-orcid":false,"given":"Matthias","family":"Fellner","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Biomedical Sciences, University of Otago, P.O. Box 56, 710 Cumberland St., Dunedin 9054, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abigail E.","family":"Burgess","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Biomedical Sciences, University of Otago, P.O. Box 56, 710 Cumberland St., Dunedin 9054, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2175-9537","authenticated-orcid":false,"given":"Peter D.","family":"Mace","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Biomedical Sciences, University of Otago, P.O. Box 56, 710 Cumberland St., Dunedin 9054, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.3389\/fonc.2012.00026","article-title":"Histone ubiquitination and deubiquitination in transcription, DNA damage response, and cancer","volume":"2","author":"Cao","year":"2012","journal-title":"Front. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1146\/annurev.biochem.70.1.503","article-title":"Mechanisms underlying ubiquitination","volume":"70","author":"Pickart","year":"2001","journal-title":"Annu. Rev. 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