Journal
CELLULAR SIGNALLING
Volume 26, Issue 5, Pages 1089-1097Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2014.01.028
Keywords
GATA-2; Smad4; TGF-beta signaling pathway; Erythroid differentiation
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Funding
- Chinese National Natural Science Foundation Projects [81070392, 81222005]
- Special Funds for Major State Basic Research of China [2012AA020206, 2013CB910800]
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GATA-2, a member of zinc finger GATA transcription factor family, plays key role in the hematopoietic stem cells self-renewal and differentiation. The transforming growth factor-beta(TGF beta) signaling pathway is a major signaling network that controls cell proliferation, differentiation and tumor suppression. Here we found that GATA-2 negatively regulated TGF-beta signaling pathway in Smad4-dependent manner. GATA-2 specifically interacts with Smad4 with its N-terminal while the zinc finger domain of GATA-2 is essential for negative regulation of TGF beta. Although GATA-2 did not affect the phosphorylation of Smad2/3 and the complex Smad2/3/4 formation in response to TG beta, the DNA binding activity of Smad4 was decreased significantly by GATA-2 overexpression. Overexpression of GATA-2 in K562 cells led to reduced TGF beta-induced erythroid differentiation while knockdown of GATA-2 enhanced TGF beta-induced erythroid differentiation. All these results suggest that GATA-2 is a novel negative regulator of TGF beta signal pathway. (C) 2014 Elsevier Inc All rights reserved.
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