An emerging model for BAP1's role in regulating cell cycle progression.
An emerging model for BAP1's role in regulating cell cycle progression.
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BAP1在调节细胞周期进程中的作用的新兴模型。
DOI：
10.1007/s12013-011-9184-6
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发表时间：
2011-06
影响因子：
2.6
通讯作者：
Wilkinson, Keith D.
中科院分区：
文献类型：
--
作者：
Eletr, Ziad M.;Wilkinson, Keith D.
BRCA 1相关蛋白-1（BAP 1）是一种729个残基的核定位去泛素化酶（DUB），在BAP 1缺失的NCI-H226肺癌细胞系中显示肿瘤抑制特性。改变BAP 1细胞水平或酶活性的研究报告了细胞周期进展的缺陷，特别是在G1/S转换。最近，BAP 1被证明与转录调节因子宿主细胞因子1（HCF-1）相关。BAP 1/HCF-1相互作用由HCF-1 Kelch结构域和BAP 1内的HCF-1结合基序（HBM）介导。HCF-1在体内被泛素修饰，异位研究表明BAP 1使HCF-1去泛素化。HCF-1是一种染色质相关蛋白，被认为通过将适当的组蛋白修饰酶连接到转录因子的子集来激活和抑制转录。HCF-1的一个已知作用是通过将H3 K4组蛋白甲基转移酶募集到E2 F1转录因子来促进细胞周期在G1/S边界的进展，使得S期所需的基因可以被转录。考虑到BAP 1/HCF-1和HCF-1/E2 F之间的强关联，可以合理地推测BAP 1通过共调节HCF-1/E2 F控制的启动子的转录来影响G1/S期的细胞增殖
BRCA1-associated protein-1 (BAP1) is a 729 residue, nuclear-localized deubiquitinating enzyme (DUB) that displays tumor suppressor properties in the BAP1-null NCI-H226 lung carcinoma cell line. Studies that have altered BAP1 cellular levels or enzymatic activity have reported defects in cell cycle progression, notably at the G1/S transition. Recently BAP1 was shown to associate with the transcriptional regulator host cell factor 1 (HCF-1). The BAP1/HCF-1 interaction is mediated by the HCF-1 Kelch domain and an HCF-1 binding motif (HBM) within BAP1. HCF-1 is modified with ubiquitin in vivo, and ectopic studies suggest BAP1 deubiquitinates HCF-1. HCF-1 is a chromatin-associated protein thought to both activate and repress transcription by linking appropriate histone-modifying enzymes to a subset of transcription factors. One known role of HCF-1 is to promote cell cycle progression at the G1/S boundary by recruiting H3K4 histone methyltransferases to the E2F1 transcription factor so that genes required for S-phase can be transcribed. Given the robust associations between BAP1/HCF-1 and HCF-1/E2Fs, it is reasonable to speculate that BAP1 influences cell proliferation at G1/S by co-regulating transcription from HCF-1/E2F-governed promoters
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