The BRCA1 Breast Cancer Suppressor: Regulation of Transport, Dynamics, and Function at Multiple Subcellular Locations.
The BRCA1 Breast Cancer Suppressor: Regulation of Transport, Dynamics, and Function at Multiple Subcellular Locations.
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DOI：
10.6064/2012/796808
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发表时间：
2012
期刊：
影响因子：
3.2
通讯作者：
Henderson BR
中科院分区：
文献类型：
--
作者：
Henderson BR
BRCA 1基因中的遗传突变使乳腺癌/卵巢癌的风险更高。BRCA 1肿瘤抑制因子是一种1863个氨基酸的蛋白质，具有多个蛋白质相互作用结构域，促进其在调节DNA修复和维持、细胞周期进展、转录和细胞存活/凋亡中的作用。BRCA 1最初被鉴定为核磷蛋白，但后来被证明含有不同的转运序列，包括核输出和核定位信号，使其能够在细胞核和细胞质内的特定位点之间穿梭，包括DNA修复灶，中心体和线粒体。BRCA 1核转运和泛素E3连接酶的酶活性受到BRCA 1二聚体结合伴侣BARD 1的严格调节，并进一步受到癌症突变和多种信号通路的调节。本文将重点介绍BRCA 1的运输，动力学和多个细胞内目的地，重点是如何调节这些事件的影响，并确定了广泛的重要细胞功能。
Inherited mutations in the BRCA1 gene predispose to a higher risk of breast/ovarian cancer. The BRCA1 tumor suppressor is a 1863 amino acid protein with multiple protein interaction domains that facilitate its roles in regulating DNA repair and maintenance, cell cycle progression, transcription, and cell survival/apoptosis. BRCA1 was first identified as a nuclear phosphoprotein, but has since been shown to contain different transport sequences including nuclear export and nuclear localization signals that enable it to shuttle between specific sites within the nucleus and cytoplasm, including DNA repair foci, centrosomes, and mitochondria. BRCA1 nuclear transport and ubiquitin E3 ligase enzymatic activity are tightly regulated by the BRCA1 dimeric binding partner BARD1 and further modulated by cancer mutations and diverse signaling pathways. This paper will focus on the transport, dynamics, and multiple intracellular destinations of BRCA1 with emphasis on how regulation of these events has impact on, and determines, a broad range of important cellular functions.