The corepressor CtBP interacts with Evi-1 to repress transforming growth factor β signaling

被引：191

作者：

Izutsu, K ^{[1
]}

Kurokawa, M ^{[1
]}

Imai, Y ^{[1
]}

Maki, K ^{[1
]}

Mitani, K ^{[1
]}

Hirai, H ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, Tokyo 1138655, Japan

来源：

BLOOD | 2001年 / 97卷 / 09期

关键词：

D O I：

10.1182/blood.V97.9.2815

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Evi-1 is a zinc finger nuclear protein whose inappropriate expression leads to leukemic transformation of hematopoietic cells in mice and humans. This was previously shown to block the antiproliferative effect of transforming growth factor beta (TGF-beta). Evi-1 represses TGF-beta signaling by direct interaction with Smad3 through its first zinc finger motif. Here, it is demonstrated that Evi-1 represses Smad-induced transcription by recruiting C-terminal binding protein (CtBP) as a corepressor. Evi-1 associates with CtBP1 through one of the consensus binding motifs, and this association is required for efficient inhibition of TGF-beta signaling, A specific inhibitor for histone deacetylase (HDAc) alleviates Evi-1-mediated repression of TGF-beta signaling, suggesting that HDAc is involved in the transcriptional repression by Evi-1. This identifies a novel function of Evi-1 as a member of corepressor complexes and suggests that aberrant recruitment of corepressors is one of the mechanisms for Evi-1-induced leukemogenesis. (Blood. 2001; 97:2815-2822) (C) 2001 by The American Society of Hematology.

引用

页码：2815 / 2822

页数：8

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