GATA-2 inhibits transforming growth factor-β signaling pathway through interaction with Smad4
| Autor: | Hui Chen, Wei-Wei Zheng, Jian Wang, Chang-Yan Li, Xiao-Ming Yang, Xiao-Ming Dong, Yu-Xin Jia, Lan Dong, En-Dong Liu, Chang-Hui Ge, Yang Yang, Hong-Mei Ning, Liu-Jun Tang, Zhi-Wei Feng, Yi-Qun Zhan, Yi-Nan Jiang, Miao Yu, Rong-Hua Yin |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Smad2 Protein
Biology Histone Deacetylases Cell Line Transforming Growth Factor beta1 Transforming Growth Factor beta TGF beta signaling pathway Humans Smad3 Protein Phosphorylation RNA Small Interfering Smad4 Protein Zinc finger Cell Differentiation DNA Hep G2 Cells Cell Biology Activins Cell biology GATA2 Transcription Factor Haematopoiesis HEK293 Cells embryonic structures GATA transcription factor RNA Interference Signal transduction Stem cell K562 Cells Protein Binding Signal Transduction Transforming growth factor |
| Zdroj: | Cellular Signalling. 26:1089-1097 |
| ISSN: | 0898-6568 |
| DOI: | 10.1016/j.cellsig.2014.01.028 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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