摘要
BRCA1-乳腺和卵巢肿瘤抑制基因,通过DNA修复功能维护基因组的稳定性、细胞周期检查点,异染色质的形成和中心体扩增。BRCA1与BARD1构成一个环二型E3泛素连接酶。BRCA1-基因相关蛋白1(BAP1)是一个去泛素酶也能调节相似的细胞活动,包括细胞周期调控,转录,染色质修饰和DNA损伤反应。BRCA1基因胚系突变易患乳腺、卵巢、输卵管、腹膜、胰腺癌和前列腺癌,并且BAP1突变结合某些类型的DNA损伤引起的恶性间皮瘤,葡萄膜和皮肤黑色素瘤、肺腺癌、肾细胞癌。虽然BAP1最初作为一种BRCA1-相关蛋白质的发现,近年来质谱扫描BAP1相互作用未能检测到BRCA1,加大了假定内生相互作用的疑惑性。然而,除了物理相互作用,新的证据表明两者之间的蛋白质的功能有相关性。本文综述了总结了BAP1功能的组蛋白修饰和损伤反应,注重BAP1的相关性BRCA1功能。BRCA1和BAP1之间的合作功能的认识可能会发现在各种相关的癌症的新药物靶点的机会。
关键词: BRCA1,BAP1,DNA损伤反应,组蛋白修饰,多梳蛋白。
Current Cancer Drug Targets
Title:Functional Link between BRCA1 and BAP1 through Histone H2A, Heterochromatin and DNA Damage Response
Volume: 16 Issue: 2
Author(s): Takayo Fukuda, Tomoko Tsuruga, Takako Kuroda, Hiroyuki Nishikawa and Tomohiko Ohta
Affiliation:
关键词: BRCA1,BAP1,DNA损伤反应,组蛋白修饰,多梳蛋白。
摘要: BRCA1, a breast and ovarian tumor suppressor, maintains genome stability through its functions in DNA repair, cell-cycle checkpoints, heterochromatin formation and centrosome amplification. BRCA1 interacts with BARD1 to constitute a RING heterodimer-type E3 ubiquitin ligase. BRCA1-associated protein 1 (BAP1) is a deubiquitinating enzyme that also regulates similar cellular events, including cell-cycle control, transcription, chromatin modification and DNA damage response. Germline mutations in BRCA1 predispose individuals to breast, ovarian, fallopian tube, peritoneal, pancreatic and prostate cancers, whereas BAP1 mutations combined with certain types of DNA damage provoke malignant mesothelioma, uveal and cutaneous melanoma, lung adenocarcinoma and renal cell carcinoma. Although BAP1 was initially discovered as a BRCA1-associated protein, recent mass-spectrometric screens of BAP1 interactors failed to detect BRCA1, raising questions about their presumed endogenous interaction. However, in addition to physical interaction, new evidence indicates a functional correlation between the two proteins. This review summarizes BAP1 function in histone modification and the DNA damage response, focusing on BAP1’s relevance to BRCA1 function. An understanding of the cooperative functions between BRCA1 and BAP1 may uncover opportunities for new drug targets in a variety of related cancers.
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Cite this article as:
Takayo Fukuda, Tomoko Tsuruga, Takako Kuroda, Hiroyuki Nishikawa and Tomohiko Ohta , Functional Link between BRCA1 and BAP1 through Histone H2A, Heterochromatin and DNA Damage Response, Current Cancer Drug Targets 2016; 16 (2) . https://dx.doi.org/10.2174/1568009615666151030102427
DOI https://dx.doi.org/10.2174/1568009615666151030102427 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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