Opposed regulation of corepressor CtBP by SUMOylation and PDZ binding
Opposed regulation of corepressor CtBP by SUMOylation and PDZ binding
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DOI：
10.1016/s1097-2765(03)00175-8
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发表时间：
2003-05-01
期刊：
影响因子：
16
通讯作者：
Feng, XH
中科院分区：
文献类型：
--
作者：
Lin, X;Sun, BH;Feng, XH
转录辅阻遏物CtBP通常通过与相互作用阻遏物中保守的PxDLS基序相互作用而被募集到靶启动子。在这项研究中，我们证明了CtBP 1是SUMO化的，它的SUMO化深刻地影响了它的亚细胞定位。SUMO化发生在CtBP 1的单个Lys残基Lys 428处。CtBP 2是CtBP 1的同源物，缺乏SUMO化位点，并且不被SUMO-1修饰。将Lys 428突变为Arg（K428 R）使CtBP 1从细胞核转移到细胞质，但对CtBP 1与PxDLS基序的相互作用几乎没有影响。与定位的变化一致，K428 R突变消除了CtBP 1抑制E-钙粘蛋白启动子活性的能力。值得注意的是，SUMO化的CtBP 1抑制的PDZ结构域的nNOS，与已知的抑制作用nNOS对CtBP 1的核积累。本研究确定SUMO化作为CtBP 1依赖性转录抑制的调控机制。
The transcription corepressor CtBP is often recruited to the target promoter via interaction with a conserved PxDLS motif in the interacting repressor. In this study, we demonstrate that CtBP1 was SUMOylated and that its SUMOylation profoundly affected its subcellular localization. SUMOylation occurred at a single Lys residue, Lys428, of CtBP1. CtBP2, a close homolog of CtBP1, lacked the SUMOylation site and was not modified by SUMO-1. Mutation of Lys428 into Arg (K428R) shifted CtBP1 from the nucleus to the cytoplasm, while it had little effect on its interaction with the PxDLS motif. Consistent with a change in localization, the K428R mutation abolished the ability of CtBP1 to repress the E-cadherin promoter activity. Notably, SUMOylation of CtBP1 was inhibited by the PDZ domain of nNOS, correlating with the known inhibitory effect of nNOS on the nuclear accumulation of CtBP1. This study identifies SUMOylation as a regulatory mechanism underlying CtBP1-dependent transcriptional repression.