BAP1: Not just a BRCA1-associated protein.
BAP1: Not just a BRCA1-associated protein.
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BAP1：不仅是与BRCA1相关的蛋白质。
DOI：
10.1016/j.ctrv.2020.102091
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发表时间：
2020-11
影响因子：
11.8
通讯作者：
Kurzrock R
中科院分区：
文献类型：
--
作者：
Louie BH;Kurzrock R
BRCA1相关蛋白1(BAP1)是一种泛素羧基末端水解酶，是一种肿瘤抑制因子，利用其去泛素活性调节DNA损伤修复、细胞周期调控、染色质修饰、细胞程序性死亡和免疫反应等一系列过程。BAP1基因的突变通常会导致一些侵袭性癌症；主要是葡萄膜黑色素瘤、恶性间皮瘤、肾细胞癌和皮肤黑色素瘤。重要的是，BAP1基因的胚系突变已被确定为一种新的肿瘤易感综合征，增加了遗传性早发性癌症的风险。目前，BAP1基因突变癌症的治疗方案仅限于标准疗法。然而，已经提出了几种治疗途径来专门针对癌症中的BAP1改变。分子靶向的方法包括组蛋白脱乙酰酶抑制剂和EZH2抑制剂，分别靶向BAP1在染色质修饰和转录调控中的作用。由于BAP1在DNA损伤修复中的作用，PARP抑制剂和铂类化疗药物有可能靶向BAP1改变的肿瘤。最后，新出现的报告表明，癌症中BAP1的改变赋予了不同的免疫原性表型，这些表型可能对新的癌症免疫疗法特别敏感。本文就BAP1基因在肿瘤中的作用、特点和临床表现作一综述，以期对BAP1基因在癌症中的作用、特点和临床表现作一简要介绍。此外，我们还重点介绍了BAP1突变癌症已有的和正在出现的治疗方案。
BRCA1-Associated Protein 1 (BAP1) is a ubiquitin carboxy-terminal hydrolase that has been established as a tumor suppressor, utilizing its deubiquitinating activity to regulate a number of processes including DNA damage repair, cell cycle control, chromatin modification, programmed cell death, and the immune response. Mutations in the BAP1 gene commonly result in a number of aggressive cancers; predominantly uveal melanoma, malignant mesothelioma, renal cell carcinoma, and cutaneous melanoma. Importantly, germline mutations in the BAP1 gene have been established as a novel tumor predisposition syndrome, conferring an increased risk of hereditary, early-onset cancers. Current treatment options for cancers with BAP1 alterations are limited to standard therapies. However, several therapeutic avenues have been proposed to specifically target BAP1 alterations in cancer. Molecularly targeted approaches include histone deacetylase inhibitors and EZH2 inhibitors to target the role of BAP1 in chromatin modification and transcriptional regulation, respectively. PARP inhibitors and platinum chemotherapy agents have the potential to target BAP1-altered tumors, due to the role of BAP1 in DNA damage repair. Lastly, emerging reports suggest that BAP1-alterations in cancer confer distinct immunogenic phenotypes that may be particularly susceptible to novel cancer immunotherapies. This review aims to present a concise and up to date report on the BAP1 gene in cancer, surveying its functional roles, characteristics and clinical manifestations. Furthermore, we highlight the established and emerging therapeutic options for BAP1-mutated cancers.
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DOI：
10.1126/science.1194472
发表时间：
2010-12-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Harbour JW;Onken MD;Roberson ED;Duan S;Cao L;Worley LA;Council ML;Matatall KA;Helms C;Bowcock AM
通讯作者：
Bowcock AM
DOI：
10.2147/opth.s89591
发表时间：
2017
期刊：
Clinical ophthalmology (Auckland, N.Z.)
影响因子：
--
作者：
Krantz BA;Dave N;Komatsubara KM;Marr BP;Carvajal RD
通讯作者：
Carvajal RD
影响因子：
10.9
作者：
Heppt, Markus, V;Amaral, Teresa;Berking, Carola
通讯作者：
Berking, Carola
影响因子：
8.1
作者：
Gupta, Mrinali P.;Lane, Anne Marie;Kim, Ivana K.
通讯作者：
Kim, Ivana K.
影响因子：
13.8
作者：
Garfield, Erin M.;Walton, Kara E.;Gerami, Pedram
通讯作者：
Gerami, Pedram