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首页> 外文期刊>Molecular and Cellular Biology >The Ubiquitin Carboxyl Hydrolase BAP1 Forms a Ternary Complex with YY1 and HCF-1 and Is a Critical Regulator of Gene Expression
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The Ubiquitin Carboxyl Hydrolase BAP1 Forms a Ternary Complex with YY1 and HCF-1 and Is a Critical Regulator of Gene Expression

机译:泛素羧基水解酶BAP1与YY1和HCF-1形成三元复合物,是基因表达的关键调节剂

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The candidate tumor suppressor BAP1 is a deubiquitinating enzyme (DUB) involved in the regulation of cell proliferation, although the molecular mechanisms governing its function remain poorly defined. BAP1 was recently shown to interact with and deubiquitinate the transcriptional regulator host cell factor 1 (HCF-1). Here we show that BAP1 assembles multiprotein complexes containing numerous transcription factors and cofactors, including HCF-1 and the transcription factor Yin Yang 1 (YY1). Through its coiled-coil motif, BAP1 directly interacts with the zinc fingers of YY1. Moreover, HCF-1 interacts with the middle region of YY1 encompassing the glycine-lysine-rich domain and is essential for the formation of a ternary complex with YY1 and BAP1 in vivo. BAP1 activates transcription in an enzymatic-activity-dependent manner and regulates the expression of a variety of genes involved in numerous cellular processes. We further show that BAP1 and HCF-1 are recruited by YY1 to the promoter of the cox7c gene, which encodes a mitochondrial protein used here as a model of BAP1-activated gene expression. Our findings (i) establish a direct link between BAP1 and the transcriptional control of genes regulating cell growth and proliferation and (ii) shed light on a novel mechanism of transcription regulation involving ubiquitin signaling.
机译:候选肿瘤抑制因子BAP1是一种参与细胞增殖调控的去泛素化酶(DUB),尽管控制其功能的分子机制仍然不清楚。最近显示,BAP1与转录调节宿主细胞因子1(HCF-1)相互作用并去泛素化。在这里,我们显示BAP1组装包含许多转录因子和辅助因子(包括HCF-1和转录因子Yin Yang 1(YY1))的多蛋白复合物。 BAP1通过其盘绕线圈图案直接与YY1的锌指相互作用。此外,HCF-1与YY1的中间区域相互作用,该区域包含富含甘氨酸-赖氨酸的结构域,对于与YY1和BAP1在体内形成三元复合物至关重要。 BAP1以依赖酶活性的方式激活转录并调节参与许多细胞过程的多种基因的表达。我们进一步显示BAP1和HCF-1被YY1募集​​到 cox7c 基因的启动子,该基因编码此处用作BAP1激活基因表达模型的线粒体蛋白。我们的发现(i)在BAP1与调节细胞生长和增殖的基因的转录控制之间建立直接联系,并且(ii)阐明涉及泛素信号传导的新型转录调节机制。

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