Region 752-761 of STAT3 is critical for SRC-1 recruitment and Ser727 phosphorylation

被引：11

作者：

Zhao, H ^{[1
]}

Nakajima, R ^{[1
]}

Kunimoto, H ^{[1
]}

Sasaki, T ^{[1
]}

Kojima, H ^{[1
]}

Nakajima, K ^{[1
]}

机构：

[1] Osaka City Univ, Grad Sch Med, Dept Immunol, Abeno Ku, Osaka 5458585, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2004年 / 325卷 / 02期

关键词：

STAT3; transcription; SRC-1; phosphorylation; ChIP; RNAi; histone acetylation; RNA polymerase II; coactivator; IL-6;

D O I：

10.1016/j.bbrc.2004.10.075

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

STAT3 regulates many target genes in response to cytokines and growth factors. To study the mechanisms of STAT3-dependent transcription, we established several cell lines in which HepG2-STAT3-knockdown cells were reconstituted with a variety of STAT3 mutants. Using these cell lines, we found that truncated STAT3(1-750), but not STAT3(1-761), could not recruit SRC-1/NcoA-1 and was not hosphorylated on Ser727. Furthermore, mutation of STAT3 L755 and F757 to alanines caused the loss of STAT3-dependent SRC-1 recruitment, leaving Ser727 phosphorylation intact. Consistent with this, the STAT3-L755A/F757A mutant showed no increase in acetylated historic H3 at Lys14 and a decreased level of RNA polymerase II recruited to the target gene promoter, although p300 recruitment and historic H4 acetylation were intact. This mutant also lost responsiveness to co-expressed SRC-1. Thus, the conserved STAT3 region from 752 to 761, called STAT3 CR2, plays critical roles in STAT3-dependent transcription by recruiting SRC-1 and allowing Ser727 phosphorylation. (C) 2004 Elsevier Inc. All riahts reserved.

引用

页码：541 / 548

页数：8