TAILIEUCHUNG - Báo cáo Y học: The Ikaros family protein Eos associates with C-terminal-binding protein corepressors

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 relatedmotif PEDLA, and we demonstrate that CtBP can bind this site weakly but that it also contacts additional regions of Eos | Eur. J. Biochem. 269 5885-5892 2002 FEBS 2002 doi The Ikaros family protein Eos associates with C-terminal-binding protein corepressors Jose Perdomo and Merlin Crossley Department of Biochemistry G08 University of Sydney NSW Australia 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. Keywords corepressors gene regulation Ikaros repression transcription. The zinc finger transcription factor Ikaros was originally identified as a DNA-binding protein that recognized a critical regulatory region of the T cell-restricted CD3Ỗ gene 1 . Ikaros expression is confined to erythroid and myeloid precursors in the early stages of differentiation and to the lymphoid compartment in the adult 2 3 . The Ikaros gene codes for a protein with six zinc fingers that comply with the Kruppel C2-H2 consensus. The N-terminal fingers are involved in sequence-specific DNA binding 4 while the two zinc fingers that form the C-terminal domain mediate homodimerization 5 . Alternative mRNA splicing generates at least eight isoforms Ik-1 to Ik-8 containing subsets of the N-terminal fingers and all .

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