Perdomo José, Crossley Merlin
Department of Biochemistry, G08, University of Sydney, NSW, Australia.
Eur J Biochem. 2002 Dec;269(23):5885-92. doi: 10.1046/j.1432-1033.2002.03313.x.
Eos is a zinc finger transcription factor of the Ikaros family. It binds typical GGGAA Ikaros recognition sites in DNA and functions as a transcriptional repressor. Here we show that Eos associates with the corepressor C-terminal-binding protein (CtBP). CtBP has previously been shown to bind Pro-X-Asp-Leu-Ser (PXDLS) motifs in several DNA-binding proteins. We note that Eos contains a related motif PEDLA, and we demonstrate that CtBP can bind this site weakly but that it also contacts additional regions of Eos. Consistent with this finding, mutation of the PEDLA motif does not negate CtBP binding or CtBP-mediated repression by Eos. CtBP has previously been shown to bind to a PXDLS-type motif in Ikaros, and we show that another Ikaros-related protein TRPS1 also contains a PXDLS CtBP contact motif within its repression domain. We conclude that several Ikaros family proteins utilize CtBP corepressors to inhibit gene expression.
Eos是Ikaros家族的一种锌指转录因子。它与DNA中的典型GGGAA Ikaros识别位点结合，并作为转录抑制因子发挥作用。在此我们表明，Eos与共抑制因子C末端结合蛋白（CtBP）相关联。此前已表明CtBP可与多种DNA结合蛋白中的Pro-X-Asp-Leu-Ser（PXDLS）基序结合。我们注意到Eos含有一个相关基序PEDLA，并且我们证明CtBP可与该位点弱结合，但它也与Eos的其他区域相互作用。与这一发现一致，PEDLA基序的突变并不消除CtBP的结合或Eos介导的CtBP抑制作用。此前已表明CtBP可与Ikaros中的一个PXDLS型基序结合，并且我们表明另一种与Ikaros相关的蛋白TRPS1在其抑制结构域内也含有一个PXDLS CtBP接触基序。我们得出结论，几种Ikaros家族蛋白利用CtBP共抑制因子来抑制基因表达。
