Ikaros interactions with CtBP reveal a repression mechanism that is independent of histone deacetylase activity
Ikaros interactions with CtBP reveal a repression mechanism that is independent of histone deacetylase activity
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DOI：
10.1074/jbc.m000254200
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发表时间：
2000-06-30
影响因子：
4.8
通讯作者：
Georgopoulos, K
中科院分区：
文献类型：
--
作者：
Koipally, J;Georgopoulos, K
我们以前已经表明，Ikaros可以通过组蛋白脱乙酰酶复合物的招聘抑制转录。在这里，我们提供的证据表明，Ikaros也可以抑制转录通过其与辅阻遏物，C-末端结合蛋白（CtBP）的相互作用。CtBP通过存在于这些蛋白质的N末端的PEDLS基序与Ikaros同种型相互作用，但不与缺乏该基序的同源物如Aiolos相互作用。Ikaros中阻止CtBP相互作用的突变降低了其抑制转录的能力，CtBP与Sin 3A相互作用，但不与Mi-2共阻遏物相互作用，并且其以不依赖于组蛋白脱乙酰酶活性的方式抑制转录。这些数据有力地表明，CtBP有助于组蛋白脱乙酰酶活性独立的Ikaros抑制机制。最后，我们发现，病毒癌蛋白E1 A，它结合到CtBP，也显示出与Ikaros强关联。这种Ikaros-E1 A相互作用可能是Ikaros在E1 A转化细胞中抑制转录的能力降低的基础。
We have previously shown that Ikaros can repress transcription through the recruitment of histone deacetylase complexes. Here we provide evidence that Ikaros can also repress transcription through its interactions with the co-repressor, C-terminal binding protein (CtBP). CtBP interacts with Ikaros isoforms through a PEDLS motif present at the N terminus of these proteins but not with homologues like Aiolos which lack this motif. Mutations in Ikaros that prevent CtBP interactions reduce its ability to repress transcription, CtBP interacts with Sin3A but not with the Mi-2 co-repressor and it represses transcription in a manner that is independent of histone deacetylase activity. These data strongly suggest that CtBP contributes to a histone deacetylase activity independent mechanism of repression by Ikaros. Finally, we show that the viral oncoprotein E1A, which binds to CtBP, also shows a strong association with Ikaros. This Ikaros-E1A interaction may underlie Ikaros's decreased ability to repress transcription in E1A transformed cells.