Identification of a novel BTB-zinc finger transcriptional repressor, CIBZ, that interacts with CtBP corepressor
Identification of a novel BTB-zinc finger transcriptional repressor, CIBZ, that interacts with CtBP corepressor
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DOI：
10.1111/j.1365-2443.2005.00885.x
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发表时间：
2005-09-01
期刊：
影响因子：
2.1
通讯作者：
Kawaichi, M
中科院分区：
文献类型：
--
作者：
Sasai, N;Matsuda, E;Kawaichi, M
转录辅阻遏物 C 端结合蛋白 (CtBP) 被认为参与发育和肿瘤发生，但其辅阻遏物活性的调节很大程度上未知。我们在这里展示了一种新型 BTB-锌指蛋白 CIBZ（CtBP 相互作用的 BTB 锌指蛋白；最近被鉴定为 e-box/二联体结合蛋白的大鼠 ZENON 的小鼠直系同源物），将 CtBP 从间期细胞中的弥散核定位重新分配到着丝粒周围病灶。 CIBZ 通过保守的 CtBP 结合基序 PLDLR 与 CtBP 物理结合。当异源靶向 DNA 时，CIBZ 通过两个独立的抑制结构域（N 端 BTB 结构域和包含 PLDLR 基序的 RD2 区域）分别以不依赖组蛋白脱乙酰酶和依赖组蛋白脱乙酰酶的方式抑制转录。 PLDLR 基序的突变消除了 CIBZ-CtBP 相互作用和 RD2 的转录抑制活性，但不影响 BTB 结构域的抑制活性。此外，这种 PLDLR 突变的 CIBZ 不能将 CtBP 靶向着丝粒周围病灶，尽管它定位于着丝粒周围病灶本身。这些结果表明，CIBZ 介导的至少一种抑制机制是将 CtBP/HDAC 复合物募集到着丝粒周围病灶，并且 CIBZ 可能调节 CtBP 的着丝粒周围靶向。
The transcriptional corepressor C-terminal binding protein (CtBP) is thought to be involved in development and oncogenesis, but the regulation of its corepressor activity is largely unknown. We show here that a novel BTB-zinc finger protein, CIBZ (CtBP-interacting BTB zinc finger protein; a mouse ortholog of rat ZENON that was recently identified as an e-box/dyad binding protein), redistributes CtBP to pericentromeric foci from a diffuse nuclear localization in interphase cells. CIBZ physically associates with CtBP via a conserved CtBP binding motif, PLDLR. When heterologously targeted to DNA, CIBZ represses transcription via two independent repression domains, an N-terminal BTB domain and a PLDLR motif-containing RD2 region, in a histone deacetylase-independent and -dependent manner, respectively. Mutation in the PLDLR motif abolishes the CIBZ-CtBP interaction and transcriptional repression activity of RD2, but does not affect the repression activity of the BTB domain. Furthermore, this PLDLR-mutated CIBZ cannot target CtBP to pericentromeric foci, although it is localized to the pericentromeric foci itself. These results suggest that at least one repression mechanism mediated by CIBZ is recruitment of the CtBP/HDAC complex to pericentromeric foci, and that CIBZ may regulate pericentromeric targeting of CtBP.