title: GATA-2 inhibits transforming growth factor-β signaling pathway through interaction with Smad4.
abstract: 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.
authors: School of Chemical Engineering and Technology, Department of Pharmaceutical Engineering, Tianjin University, Tianjin 300072, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Xiao-Ming
authors: XM
authors: Dong
authors: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Rong-Hua
authors: RH
authors: Yin
authors: Purdue University, Department of Biological Sciences, 915W. State Street, West Lafayette, IN 47907-2054, United States.
authors: Yang
authors: Y
authors: Yang
authors: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Zhi-Wei
authors: ZW
authors: Feng
authors: Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital to Academy of Military Medical Sciences, Beijing 100071, China.
authors: Hong-Mei
authors: HM
authors: Ning
authors: Department of Anesthesiology, General Hospital of Chinese People's Armed Police Forces, Beijing, China.
authors: Lan
authors: L
authors: Dong
authors: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Wei-Wei
authors: WW
authors: Zheng
authors: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Liu-Jun
authors: LJ
authors: Tang
authors: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Jian
authors: J
authors: Wang
authors: School of Chemical Engineering and Technology, Department of Pharmaceutical Engineering, Tianjin University, Tianjin 300072, China.
authors: Yu-Xin
authors: YX
authors: Jia
authors: An Hui Medical University, Hefei 230032, China.
authors: Yi-Nan
authors: YN
authors: Jiang
authors: An Hui Medical University, Hefei 230032, China.
authors: En-Dong
authors: ED
authors: Liu
authors: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Hui
authors: H
authors: Chen
authors: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Yi-Qun
authors: YQ
authors: Zhan
authors: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Miao
authors: M
authors: Yu
authors: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Chang-Hui
authors: CH
authors: Ge
authors: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China; An Hui Medical University, Hefei 230032, China. Electronic address: fmmli@163.com.
authors: Chang-Yan
authors: CY
authors: Li
authors: School of Chemical Engineering and Technology, Department of Pharmaceutical Engineering, Tianjin University, Tianjin 300072, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China. Electronic address: xiaomingyang@sina.com.
authors: Xiao-Ming
authors: XM
authors: Yang
mesh_terms: D028341:Activins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D050989:GATA2 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D051901:Smad4 Protein / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D000099186:Histone Deacetylase 3
chemical_list: D028341:Activins; D004247:DNA; D050989:GATA2 Transcription Factor; D006655:Histone Deacetylases; D034741:RNA, Small Interfering; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000099186:Histone Deacetylase 3; C422405:activin A
keywords: Erythroid differentiation; GATA-2; Smad4; TGF-β signaling pathway