Breast cancer metastasis suppressor 1 (BRMS1) forms complexes with retinoblastoma-binding protein 1 (RBP1) and the mSin3 histone deacetylase complex and represses transcription
Breast cancer metastasis suppressor 1 (BRMS1) forms complexes with retinoblastoma-binding protein 1 (RBP1) and the mSin3 histone deacetylase complex and represses transcription
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DOI：
10.1074/jbc.m307969200
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发表时间：
2004-01-09
影响因子：
4.8
通讯作者：
Welch, DR
中科院分区：
文献类型：
--
作者：
Meehan, WJ;Samant, RS;Welch, DR
乳腺癌转移抑制因子1(BRMS1)在不抑制致瘤性的情况下抑制多种人和小鼠癌细胞的转移。通过酵母双杂交和免疫共沉淀，BRMS1在人乳腺和黑色素瘤细胞系中与视网膜母细胞瘤结合蛋白1和至少7个mSin3组蛋白脱乙酰酶(HDAC)复合体成员相互作用。在体内，当BRMS1被招募到Gal4启动子时，BRMS1共免疫共沉淀具有酶活性的HDAC蛋白并抑制转录。BRMS1存在于大的mSin3复合体中，类似于1.4-1.9的丙二醛，但也与HDAC1形成较小的复合体。缺失分析表明，BRMS1的羧基末端42个氨基酸对于与mSin3复合体的大部分相互作用并不关键，并且BRMS1似乎与该复合体有不止一个结合点。这些结果进一步表明，BRMS1可能通过与mSin3.HDAC复合体的相互作用参与转录调控，并提示了BRMS1抑制肿瘤转移的新机制。
Breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis of multiple human and murine cancer cells without inhibiting tumorigenicity. By yeast two-hybrid and co-immunoprecipitation, BRMS1 interacts with retinoblastoma binding protein 1 and at least seven members of the mSin3 histone deacetylase (HDAC) complex in human breast and melanoma cell lines. BRMS1 co-immunoprecipitates enzymatically active HDAC proteins and represses transcription when recruited to a Gal4 promoter in vivo. BRMS1 exists in large mSin3 complex(es) of similar to1.4-1.9 MDa, but also forms smaller complexes with HDAC1. Deletion analyses show that the carboxyl-terminal 42 amino acids of BRMS1 are not critical for interaction with much of the mSin3 complex and that BRMS1 appears to have more than one binding point to the complex. These results further show that BRMS1 may participate in transcriptional regulation via interaction with the mSin3.HDAC complex and suggest a novel mechanism by which BRMS1 might suppress cancer metastasis.