{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T00:51:46Z","timestamp":1793407906297,"version":"4.5.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T00:00:00Z","timestamp":1635984000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T00:00:00Z","timestamp":1635984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Pharmacol Sin"],"published-print":{"date-parts":[[2022,7]]},"DOI":"10.1038\/s41401-021-00783-5","type":"journal-article","created":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T11:37:43Z","timestamp":1636025863000},"page":"1803-1815","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["BAP1 loss augments sensitivity to BET inhibitors in cancer cells"],"prefix":"10.1038","volume":"43","author":[{"given":"Yu-yan","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong-lu","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-lian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui-ming","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-si","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-hui","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin-xuan","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-wen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-lei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,4]]},"reference":[{"key":"783_CR1","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1158\/2159-8290.CD-19-1220","volume":"10","author":"M Carbone","year":"2020","unstructured":"Carbone M, Harbour JW, Brugarolas J, Bononi A, Pagano I. Biological mechanisms and clinical significance of BAP1 mutations in human cancer. Cancer Discov. 2020;10:1103\u201320.","journal-title":"Cancer Discov"},{"key":"783_CR2","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1126\/science.aav4902","volume":"364","author":"M He","year":"2019","unstructured":"He M, Chaurushiya MS, Webster JD, Kummerfeld S, Reja R, Chaudhuri S, et al. Intrinsic apoptosis shapes the tumor spectrum linked to inactivation of the deubiquitinase BAP1. Science. 2019;364:283\u20135.","journal-title":"Science"},{"key":"783_CR3","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1002\/path.5213","volume":"247","author":"R Rabbie","year":"2019","unstructured":"Rabbie R, Ferguson P, Molina-Aguilar C, Adams D, Robles-Espinoza C. Melanoma subtypes: genomic profiles, prognostic molecular markers and therapeutic possibilities. J Pathol. 2019;247:539\u201351.","journal-title":"J Pathol"},{"key":"783_CR4","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/s41572-020-0158-0","volume":"6","author":"MJ Jager","year":"2020","unstructured":"Jager MJ, Shields CL, Cebulla CM, Abdel-Rahman MH, Grossniklaus HE, Stern MH, et al. Uveal melanoma. Nat Rev Dis Prim. 2020;6:24.","journal-title":"Nat Rev Dis Prim"},{"key":"783_CR5","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.ccell.2017.07.003","volume":"32","author":"A Robertson","year":"2017","unstructured":"Robertson A, Shih J, Yau C, Gibb E, Oba J, Mungall K, et al. Integrative analysis identifies four molecular and clinical subsets in uveal melanoma. Cancer Cell. 2017;32:204\u201320.e15.","journal-title":"Cancer Cell"},{"key":"783_CR6","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1038\/s41581-020-0301-x","volume":"16","author":"N Dizman","year":"2020","unstructured":"Dizman N, Philip E, Pal S. Genomic profiling in renal cell carcinoma. Nat Rev Nephrol. 2020;16:435\u201351.","journal-title":"Nat Rev Nephrol"},{"key":"783_CR7","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1126\/science.1194472","volume":"330","author":"JW Harbour","year":"2010","unstructured":"Harbour JW, Onken MD, Roberson ED, Duan S, Cao L, Worley LA, et al. Frequent mutation of BAP1 in metastasizing uveal melanomas. Science. 2010;330:1410\u20133.","journal-title":"Science"},{"key":"783_CR8","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/nrc3459","volume":"13","author":"M Carbone","year":"2013","unstructured":"Carbone M, Yang H, Pass HI, Krausz T, Testa JR, Gaudino G. BAP1 and cancer. Nat Rev Cancer. 2013;13:153\u20139.","journal-title":"Nat Rev Cancer"},{"key":"783_CR9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-08255-x","volume":"10","author":"A Campagne","year":"2019","unstructured":"Campagne A, Lee MK, Zielinski D, Michaud A, Le Corre S, Dingli F, et al. BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation. Nat Commun. 2019;10:348.","journal-title":"Nat Commun"},{"key":"783_CR10","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1097\/CMR.0000000000000714","volume":"31","author":"X Luo","year":"2021","unstructured":"Luo X, Xu Y, Li Y, Zhang G, Huang S, Liu X, et al. BAP1 deletion abrogates growth and metastasis of murine cutaneous melanoma. Melanoma Res. 2021;31:119\u201329.","journal-title":"Melanoma Res"},{"key":"783_CR11","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1016\/j.ccr.2014.04.017","volume":"25","author":"FX Yu","year":"2014","unstructured":"Yu FX, Luo J, Mo JS, Liu G, Kim YC, Meng Z, et al. Mutant Gq\/11 promote uveal melanoma tumorigenesis by activating YAP. Cancer Cell. 2014;25:822\u201330.","journal-title":"Cancer Cell"},{"key":"783_CR12","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1038\/nbt0816-888d","volume":"34","author":"NL Bray","year":"2016","unstructured":"Bray NL, Pimentel H, Melsted P, Pachter L. Erratum: near-optimal probabilistic RNA-seq quantification. Nat Biotechnol. 2016;34:888.","journal-title":"Nat Biotechnol"},{"key":"783_CR13","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.12688\/f1000research.7563.1","volume":"4","author":"C Soneson","year":"2015","unstructured":"Soneson C, Love MI, Robinson MD. Differential analyses for RNA-seq: transcript-level estimates improve gene-level inferences. F1000Res. 2015;4:1521.","journal-title":"F1000Res"},{"key":"783_CR14","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550.","journal-title":"Genome Biol"},{"key":"783_CR15","doi-asserted-by":"publisher","first-page":"W316","DOI":"10.1093\/nar\/gkr483","volume":"39","author":"C Xie","year":"2011","unstructured":"Xie C, Mao X, Huang J, Ding Y, Wu J, Dong S, et al. KOBAS 2.0: a web server for annotation and identification of enriched pathways and diseases. Nucleic Acids Res. 2011;39:W316\u201322.","journal-title":"Nucleic Acids Res"},{"key":"783_CR16","doi-asserted-by":"publisher","first-page":"2281","DOI":"10.1038\/nprot.2013.143","volume":"8","author":"FA Ran","year":"2013","unstructured":"Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F. Genome engineering using the CRISPR-Cas9 system. Nat Protoc. 2013;8:2281\u2013308.","journal-title":"Nat Protoc"},{"key":"783_CR17","doi-asserted-by":"publisher","first-page":"5220","DOI":"10.1038\/sj.onc.1209615","volume":"25","author":"C Giacinti","year":"2006","unstructured":"Giacinti C, Giordano A. RB and cell cycle progression. Oncogene. 2006;25:5220\u20137.","journal-title":"Oncogene"},{"key":"783_CR18","doi-asserted-by":"publisher","first-page":"16669","DOI":"10.1073\/pnas.1108190108","volume":"108","author":"JA Mertz","year":"2011","unstructured":"Mertz JA, Conery AR, Bryant BM, Sandy P, Balasubramanian S, Mele DA, et al. Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci USA. 2011;108:16669\u201374.","journal-title":"Proc Natl Acad Sci USA"},{"key":"783_CR19","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1038\/nature16508","volume":"529","author":"S Shu","year":"2016","unstructured":"Shu S, Lin CY, He HH, Witwicki RM, Tabassum DP, Roberts JM, et al. Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer. Nature. 2016;529:413\u20137.","journal-title":"Nature"},{"key":"783_CR20","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1073\/pnas.1309085110","volume":"111","author":"H Yu","year":"2014","unstructured":"Yu H, Pak H, Hammond-Martel I, Ghram M, Rodrigue A, Daou S, et al. Tumor suppressor and deubiquitinase BAP1 promotes DNA double-strand break repair. Proc Natl Acad Sci USA. 2014;111:285\u201390.","journal-title":"Proc Natl Acad Sci USA"},{"key":"783_CR21","doi-asserted-by":"publisher","first-page":"eaax1738","DOI":"10.1126\/sciadv.aax1738","volume":"5","author":"JN Kuznetsov","year":"2019","unstructured":"Kuznetsov JN, Aguero TH. BAP1 regulates epigenetic switch from pluripotency to differentiation in developmental lineages giving rise to BAP1-mutant cancers. Sci Adv. 2019;5:eaax1738.","journal-title":"Sci Adv"},{"key":"783_CR22","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1158\/1078-0432.CCR-11-0946","volume":"18","author":"S Landreville","year":"2012","unstructured":"Landreville S, Agapova OA, Matatall KA, Kneass ZT, Onken MD, Lee RS, et al. Histone deacetylase inhibitors induce growth arrest and differentiation in uveal melanoma. Clin Cancer Res. 2012;18:408\u201316.","journal-title":"Clin Cancer Res"},{"key":"783_CR23","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1038\/nrm.2016.143","volume":"18","author":"T Fujisawa","year":"2017","unstructured":"Fujisawa T, Filippakopoulos P. Functions of bromodomain-containing proteins and their roles in homeostasis and cancer. Nat Rev Mol Cell Biol. 2017;18:246\u201362.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"783_CR24","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1006\/geno.1997.5000","volume":"45","author":"MH Jones","year":"1997","unstructured":"Jones MH, Numata M, Shimane M. Identification and characterization of BRDT: a testis-specific gene related to the bromodomain genes RING3 and Drosophila fsh. Genomics. 1997;45:529\u201334.","journal-title":"Genomics"},{"key":"783_CR25","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nrd4286","volume":"13","author":"P Filippakopoulos","year":"2014","unstructured":"Filippakopoulos P, Knapp S. Targeting bromodomains: epigenetic readers of lysine acetylation. Nat Rev Drug Discov. 2014;13:337\u201356.","journal-title":"Nat Rev Drug Discov"},{"key":"783_CR26","doi-asserted-by":"publisher","first-page":"33397","DOI":"10.18632\/oncotarget.5179","volume":"6","author":"G Ambrosini","year":"2015","unstructured":"Ambrosini G, Sawle AD, Musi E, Schwartz GK. BRD4-targeted therapy induces Myc-independent cytotoxicity in Gnaq\/11-mutatant uveal melanoma cells. Oncotarget. 2015;6:33397\u2013409.","journal-title":"Oncotarget"},{"key":"783_CR27","doi-asserted-by":"publisher","first-page":"19408","DOI":"10.1073\/pnas.1216363109","volume":"109","author":"WW Lockwood","year":"2012","unstructured":"Lockwood WW, Zejnullahu K, Bradner JE, Varmus H. Sensitivity of human lung adenocarcinoma cell lines to targeted inhibition of BET epigenetic signaling proteins. Proc Natl Acad Sci USA. 2012;109:19408\u201313.","journal-title":"Proc Natl Acad Sci USA"},{"key":"783_CR28","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1038\/nbt.2776","volume":"32","author":"L Anders","year":"2014","unstructured":"Anders L, Guenther MG, Qi J, Fan ZP, Marineau JJ, Rahl PB, et al. Genome-wide localization of small molecules. Nat Biotechnol. 2014;32:92\u20136.","journal-title":"Nat Biotechnol"},{"key":"783_CR29","doi-asserted-by":"publisher","first-page":"487","DOI":"10.2217\/epi.14.91","volume":"7","author":"M Jung","year":"2015","unstructured":"Jung M, Gelato KA, Fern\u00e1ndez-Montalv\u00e1n A, Siegel S, Haendler B. Targeting BET bromodomains for cancer treatment. Epigenomics. 2015;7:487\u2013501.","journal-title":"Epigenomics"},{"key":"783_CR30","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1016\/j.molcel.2018.11.006","volume":"73","author":"JP Lambert","year":"2019","unstructured":"Lambert JP, Picaud S, Fujisawa T, Hou H, Savitsky P, Uusk\u00fcla-Reimand L, et al. Interactome Rewiring Following Pharmacological Targeting of BET Bromodomains. Mol Cell. 2019;73:621\u201338.e17.","journal-title":"Mol Cell"},{"key":"783_CR31","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1038\/nm.3947","volume":"21","author":"LM Lafave","year":"2015","unstructured":"Lafave LM, B\u00e9guelin W, Koche R, Teater M, Spitzer B, Chramiec A, et al. Loss of BAP1 function leads to EZH2-dependent transformation. Nat Med. 2015;21:1344\u20139.","journal-title":"Nat Med"},{"key":"783_CR32","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/nm.4098","volume":"22","author":"M Schoumacher","year":"2016","unstructured":"Schoumacher M, Le Corre S, Houy A, Mulugeta E, Stern MH, Roman-Roman S, et al. Uveal melanoma cells are resistant to EZH2 inhibition regardless of BAP1 status. Nat Med. 2016;22:577\u20138.","journal-title":"Nat Med"},{"key":"783_CR33","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1038\/jid.2014.528","volume":"135","author":"R Kumar","year":"2015","unstructured":"Kumar R, Taylor M, Miao B, Ji Z, Njauw JC, J\u00f6nsson G, et al. BAP1 has a survival role in cutaneous melanoma. J Invest Dermatol. 2015;135:1089\u201397.","journal-title":"J Invest Dermatol"},{"key":"783_CR34","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1080\/15384101.2019.1597506","volume":"18","author":"Y Zhang","year":"2019","unstructured":"Zhang Y, Koppula P, Gan B. Regulation of H2A ubiquitination and SLC7A11 expression by BAP1 and PRC1. Cell Cycle. 2019;18:773\u201383.","journal-title":"Cell Cycle"},{"key":"783_CR35","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1158\/0008-5472.CAN-17-1805","volume":"78","author":"J Shen","year":"2018","unstructured":"Shen J, Li P, Shao X, Yang Y, Liu X, Feng M, et al. The E3 ligase RING1 targets p53 for degradation and promotes cancer cell proliferation and survival. Cancer Res. 2018;78:359\u201371.","journal-title":"Cancer Res"},{"key":"783_CR36","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1387\/ijdb.082690mv","volume":"53","author":"M Vidal","year":"2009","unstructured":"Vidal M. Role of polycomb proteins Ring1A and Ring1B in the epigenetic regulation of gene expression. Int J Dev Biol. 2009;53:355\u201370.","journal-title":"Int J Dev Biol"},{"key":"783_CR37","doi-asserted-by":"publisher","first-page":"Fso372","DOI":"10.4155\/fsoa-2018-0115","volume":"5","author":"A Alqahtani","year":"2019","unstructured":"Alqahtani A, Choucair K, Ashraf M, Hammouda DM, Alloghbi A, Khan T, et al. Bromodomain and extra-terminal motif inhibitors: a review of preclinical and clinical advances in cancer therapy. Future Sci OA. 2019;5:Fso372.","journal-title":"Future Sci OA"},{"key":"783_CR38","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1038\/bjc.2014.417","volume":"111","author":"H Kalirai","year":"2014","unstructured":"Kalirai H, Dodson A, Faqir S, Damato BE, Coupland SE. Lack of BAP1 protein expression in uveal melanoma is associated with increased metastatic risk and has utility in routine prognostic testing. Br J Cancer. 2014;111:1373\u201380.","journal-title":"Br J Cancer"}],"container-title":["Acta Pharmacologica Sinica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41401-021-00783-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41401-021-00783-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41401-021-00783-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T07:38:18Z","timestamp":1656920298000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41401-021-00783-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,4]]},"references-count":38,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["783"],"URL":"https:\/\/doi.org\/10.1038\/s41401-021-00783-5","relation":{},"ISSN":["1671-4083","1745-7254"],"issn-type":[{"value":"1671-4083","type":"print"},{"value":"1745-7254","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,4]]},"assertion":[{"value":"15 April 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 September 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 November 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}