GATA-2 inhibits transforming growth factor-β signaling pathway through interaction with Smad4

Xiao-Ming Dong, Rong-Hua Yin, Yang Yang, Zhi-Wei Feng, Hong-Mei Ning, Lan Dong, Wei-Wei Zheng, Liu-Jun Tang, Jian Wang, Yu-Xin Jia, Yi-Nan Jiang, En-Dong Liu, Hui Chen, Yi-Qun Zhan, Miao Yu, Chang-Hui Ge, Chang-Yan Li, Xiao-Ming Yang
Cellular Signalling 2014, 26 (5): 1089-97
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-β (TGFβ) signaling pathway is a major signaling network that controls cell proliferation, differentiation and tumor suppression. Here we found that GATA-2 negatively regulated TGF-β 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 TGFβ. Although GATA-2 did not affect the phosphorylation of Smad2/3 and the complex Smad2/3/4 formation in response to TGFβ, the DNA binding activity of Smad4 was decreased significantly by GATA-2 overexpression. Overexpression of GATA-2 in K562 cells led to reduced TGFβ-induced erythroid differentiation while knockdown of GATA-2 enhanced TGFβ-induced erythroid differentiation. All these results suggest that GATA-2 is a novel negative regulator of TGFβ signal pathway.

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