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DOI | 10.1126/science.aav4902 |
Intrinsic apoptosis shapes the tumor spectrum linked to inactivation of the deubiquitinase BAP1 | |
He, Meng1; Chaurushiya, Mira S.1,6; Webster, Joshua D.2; Kummerfeld, Sarah3,7; Reja, Rohit3; Chaudhuri, Subhra4; Chen, Ying-Jiun4; Modrusan, Zora4; Haley, Benjamin4; Dugger, Debra L.1; Eastham-Anderson, Jeffrey2; Lau, Shari2; Dey, Anwesha5; Caothien, Roger4; Roose-Girma, Merone4; Newton, Kim1; Dixit, Vishva M.1 | |
2019-04-19 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 364期号:6437页码:283-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Australia |
英文摘要 | Malignancies arising from mutation of tumor suppressors have unexplained tissue proclivity. For example, BAP1 encodes a widely expressed deubiquitinase for histone H2A, but germline mutations are predominantly associated with uveal melanomas and mesotheliomas. We show that BAP1 inactivation causes apoptosis in mouse embryonic stem cells, fibroblasts, liver, and pancreatic tissue but not in melanocytes and mesothelial cells. Ubiquitin ligase RNF2, which silences genes by monoubiquitinating H2A, promoted apoptosis in BAP1-deficient cells by suppressing expression of the prosurvival genes Bcl2 and Mcl1. In contrast, BAP1 loss in melanocytes had little impact on expression of prosurvival genes, instead inducing Mitf. Thus, BAP1 appears to modulate gene expression by countering H2A ubiquitination, but its loss only promotes tumorigenesis in cells that do not engage an RNF2-dependent apoptotic program. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000464956600050 |
WOS关键词 | MUTATIONS PREDISPOSE ; GERMLINE MUTATION ; UVEAL MELANOMA ; MUTANTS ; RING1B ; GENE |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/201247 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Genentech Inc, Dept Physiol Chem, 1 DNA Way, San Francisco, CA 94080 USA; 2.Genentech Inc, Dept Pathol, 1 DNA Way, San Francisco, CA 94080 USA; 3.Genentech Inc, Dept Bioinformat, 1 DNA Way, San Francisco, CA 94080 USA; 4.Genentech Inc, Dept Mol Biol, 1 DNA Way, San Francisco, CA 94080 USA; 5.Genentech Inc, Dept Discovery Oncol, 1 DNA Way, San Francisco, CA 94080 USA; 6.5AM Ventures, 501 2nd St 350, San Francisco, CA 94107 USA; 7.Garvan Inst Med Res, Kinghorn Ctr Clin Genom, 384 Victoria St, Darlinghurst, NSW 2010, Australia |
推荐引用方式 GB/T 7714 | He, Meng,Chaurushiya, Mira S.,Webster, Joshua D.,et al. Intrinsic apoptosis shapes the tumor spectrum linked to inactivation of the deubiquitinase BAP1[J]. SCIENCE,2019,364(6437):283-+. |
APA | He, Meng.,Chaurushiya, Mira S..,Webster, Joshua D..,Kummerfeld, Sarah.,Reja, Rohit.,...&Dixit, Vishva M..(2019).Intrinsic apoptosis shapes the tumor spectrum linked to inactivation of the deubiquitinase BAP1.SCIENCE,364(6437),283-+. |
MLA | He, Meng,et al."Intrinsic apoptosis shapes the tumor spectrum linked to inactivation of the deubiquitinase BAP1".SCIENCE 364.6437(2019):283-+. |
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