Corepressor SMRT binds the BTB/POZ repressing domain of the LAZ3/BCL6 oncoprotein
Corepressor SMRT binds the BTB/POZ repressing domain of the LAZ3/BCL6 oncoprotein
复制标题
辅阻遏物 SMRT 结合 LAZ3/BCL6 癌蛋白的 BTB/POZ 抑制结构域
DOI：
10.1073/pnas.94.20.10762
复制
发表时间：
1997-09-30
影响因子：
11.1
通讯作者：
Leprince, D
中科院分区：
文献类型：
--
作者：
Dhordain, P;Albagli, O;Leprince, D
LAZ 3/BCL 6（淋巴瘤相关锌指3/B细胞淋巴瘤6）基因在非霍奇金淋巴瘤中经常发生改变。它编码一个序列特异性的DNA结合转录抑制因子，该转录抑制因子包含一个保守的N端结构域，称为BTB/POZ（bric-a-brac tramtrack broad complex/pox viruses and zinc fingers）。SMRT最初被鉴定为无配体视黄酸和甲状腺受体的辅抑制子，并与酵母转录抑制子Sin 3和HDAC-1组蛋白脱乙酰酶的哺乳动物同源物形成抑制复合物。蛋白结合试验证明LAZ 3/BCL 6 BTB/POZ结构域在体外直接与SMRT相互作用。此外，DNA结合的LAZ 3/BCL 6在体内招募SMRT，并且两种过表达的蛋白质完全共定位于核点中。最后，SMRT的过表达增强LAZ 3/BCL 6介导的抑制。这些结果将SMRT定义为LAZ 3/BCL 6的辅阻遏物，并表明LAZ 3/BCL 6和核激素受体通过涉及SMRT募集和组蛋白脱乙酰化的共同机制抑制转录。
The LAZ3/BCL6 (lymphoma-associated zinc finger 3/B cell lymphomas 6) gene frequently is altered in non-Hodgkin lymphomas. It encodes a sequence-specific DNA binding transcriptional repressor that-contains a conserved N-terminal domain, termed BTB/POZ (bric-a-brac tramtrack broad complex/pox viruses and zinc fingers), Using a yeast two-hybrid screen, we show here that the LAZ3/BCL6 BTB/POZ domain interacts with the SMRT (silencing mediator of retinoid and thyroid receptor) protein. SMRT originally was identified as a corepressor of unliganded retinoic acid and thyroid receptors and forms a repressive complex with a mammalian homolog of the yeast transcriptional repressor SIN3 and the HDAC-1 histone deacetylase. Protein binding assays demonstrate that the LAZ3/BCL6 BTB/POZ domain directly interacts with SMRT in vitro. Furthermore, DNA-bound LAZ3/BCL6 recruits SMRT in vivo, and both overexpressed proteins completely colocalize in nuclear dots, Finally, overexpression of SMRT enhances the LAZ3/BCL6-mediated repression. These results define SMRT as a corepressor of LAZ3/BCL6 and suggest that LAZ3/BCL6 and nuclear hormone receptors repress transcription through shared mechanisms involving SMRT recruitment and histone deacetylation.