Role of the BCA2 ubiquitin E3 ligase in hormone responsive breast cancer.
Role of the BCA2 ubiquitin E3 ligase in hormone responsive breast cancer.
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DOI：
10.2174/1874079001003010116
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Seth AK
中科院分区：
文献类型：
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作者：
Burger AM;Kona F;Amemiya Y;Gao Y;Bacopulos S;Seth AK
BCA 2蛋白在N端附近含有一个RING H2指和一个Zn指，并具有E3连接酶活性。RING指蛋白在介导泛素和泛素样修饰物转移到异源底物以及RING指蛋白本身中起关键作用。泛素和小泛素相关修饰物（SUMO）对蛋白质的修饰在蛋白质稳态中起着关键作用，并且对调节基本细胞过程如增殖、分化、凋亡、细胞内信号传导和基因转录调节至关重要。加入泛素或SUMO可以调节蛋白质与其伴侣相互作用的能力，改变其亚细胞定位模式并控制其稳定性。很明显，SUMO影响许多不同的生物过程，但最近的数据表明，它在转录调控中特别重要。BCA 2是一种E3连接酶，与SUMO结合酶Ubc9相互作用。因此，它可以作为一个E3的sumoylation的各种转录因子。我们发现，在635例乳腺癌患者中，74%的ER阳性浸润性导管癌中BCA2与雌激素受体共表达（p = 0.004）。在细胞水平上，BCA 2与ER共定位，并且在转录水平上，BCA 2 mRNA表达似乎受雌激素调节。BCA 2启动子区域的生物信息学分析揭示了ER和PR结合位点以及其他更一般的转录因子。本文提供的数据概述了BCA2在激素反应性乳腺癌中的潜在参与，并开辟了更好地理解ER表达调控、乳腺癌细胞生长和BCA2重要性的途径。
The BCA2 protein contains a RING H2 finger and a Zn finger near the N-terminus and has E3 ligase activity. RING finger proteins play critical roles in mediating the transfer of ubiquitin and ubiquitin like modifiers to heterologous substrates as well as to the RING finger proteins themselves. Protein modification by ubiquitin and small ubiquitin-related modifier (SUMO) plays a pivotal role in protein homeostasis and is critical to regulating basic cellular processes such as proliferation, differentiation, apoptosis, intracellular signaling, and gene-transcriptional regulation. The addition of ubiquitin or SUMO can modulate the ability of proteins to interact with their partners, alter their patterns of sub-cellular localization and control their stability. It is clear that SUMO influences many different biological processes however recent data suggest that it is specifically important in the regulation of transcription. BCA2 is an E3 ligase that interacts with the SUMO conjugating enzyme Ubc9. It could therefore function as an E3 in the sumoylation of various transcription factors. We have found that the BCA2 is co-expressed with the estrogen receptor in 74% of ER-positive invasive ductal carcinomas from a 635 member breast cancer cohort (p = 0.004). At the cellular level, BCA2 co-localizes with ER and it appears that at the transcriptional level BCA2 mRNA expression is regulated by estrogen. Bioinformatic analysis of the BCA2 promoter region revealed ER and PR binding sites as well as that of other more general transcription factors. The data presented here provides an overview of the potential involvement of the BCA2 in hormone responsive breast cancer and opens up avenues that should be exploited to better understand the regulation of ER expression, growth of breast cancer cells, and the importance of BCA2.