Transcriptional regulation of a novel BTB-zinc finger protein GetB (CIBZ)

转录辅阻遏子C末端结合蛋白(CtBP)被认为参与了肿瘤的发生和发展，但其辅阻遏子活性的调节在很大程度上是未知的。我们在这里展示了一种新的BTB-锌指蛋白，CIBZ(CtBP相互作用的BTB锌指蛋白)，它将CtBP从间期细胞的弥漫性核定位重新分布到着丝粒周围。CIBZ通过保守的CtBP结合基序PLDLR与CtBP发生物理结合。当异源靶向DNA时，CIBZ通过两个独立的抑制结构域，N-末端的BTB结构域和含有PLDLR基序的RD2区域，分别以组蛋白脱乙酰基酶不依赖和依赖的方式抑制转录。PLDLR基序的突变取消了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。这些结果提示，CIBZ介导的至少一种抑制机制是将CtBP/HDAC复合体募集到跨着丝粒中心，CIBZ可能调节CtBP的跨着丝粒靶向。

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), 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 perioentromeric foci, and that CIBZ may regulate pericentromeric targeting of CtBP.