乳腺癌转移抑制因子1（BRMS1）由热休克蛋白90（Hsp90）伴侣蛋白稳定。
Breast cancer metastasis suppressor 1 (BRMS1) is stabilized by the Hsp90 chaperone.
作者信息
Hurst Douglas R, Mehta Alka, Moore Blake P, Phadke Pushkar A, Meehan William J, Accavitti Mary Ann, Shevde Lalita A, Hopper James E, Xie Yi, Welch Danny R, Samant Rajeev S
机构信息
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
出版信息
Biochem Biophys Res Commun. 2006 Oct 6;348(4):1429-35. doi: 10.1016/j.bbrc.2006.08.005. Epub 2006 Aug 10.
Breast cancer metastasis suppressor 1 (BRMS1) is a member of the mSin3-HDAC transcription co-repressor complex. However, the proteins associated with BRMS1 have not been fully identified. Yeast two-hybrid screen, immuno-affinity chromatography, and co-immunoprecipitation experiments were performed to identify BRMS1 interacting proteins (BIPs). In addition to known core mSin3 transcriptional complex components RBBP1 and mSDS3, BRMS1 interacted with other proteins including three chaperones: DNAJB6 (MRJ), Hsp90, and Hsp70. Hsp90 is a known target of HDAC6 and reversible acetylation is one of the mechanisms that is implicated in regulation of Hsp90 chaperone complex activity. BRMS1 interacted with class II HDACs, HDAC 4, 5, and 6. We further found that BRMS1 is stabilized by Hsp90, and its turnover is proteasome dependent. The stability of BRMS1 protein may be important in maintaining the functional role of BRMS1 in metastasis suppression.
乳腺癌转移抑制因子1（BRMS1）是mSin3 - HDAC转录共抑制复合物的成员。然而，与BRMS1相关的蛋白质尚未完全鉴定出来。进行了酵母双杂交筛选、免疫亲和色谱和免疫共沉淀实验，以鉴定与BRMS1相互作用的蛋白质（BIPs）。除了已知的mSin3转录复合物核心成分RBBP1和mSDS3外，BRMS1还与其他蛋白质相互作用，包括三种分子伴侣：DNAJB6（MRJ）、热休克蛋白90（Hsp90）和热休克蛋白70（Hsp70）。Hsp90是HDAC6的已知靶点，可逆乙酰化是参与调节Hsp90分子伴侣复合物活性的机制之一。BRMS1与II类组蛋白去乙酰化酶（HDAC）4、5和6相互作用。我们进一步发现，BRMS1由Hsp90稳定，其周转依赖于蛋白酶体。BRMS1蛋白的稳定性对于维持BRMS1在转移抑制中的功能作用可能很重要。
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