2. Academic Validation
  3. Pokemon (FBI-1) interacts with Smad4 to repress TGF-β-induced transcriptional responses

Pokemon (FBI-1) interacts with Smad4 to repress TGF-β-induced transcriptional responses

  • Biochim Biophys Acta. 2015 Mar;1849(3):270-81. doi: 10.1016/j.bbagrm.2014.12.008.
Yutao Yang 1,  Jiajun Cui 2,  Feng Xue 3,  Chuanfu Zhang 4,  Zhu Mei 5,  Yue Wang 6,  Mingjun Bi 7,  Dapeng Shan 8,  Alex Meredith 7,  Hui Li 9,  Zhi-Qing David Xu 10
Affiliations

Affiliations

  • 1 Department of Neurobiology, Beijing Key Laboratory of Major Brain Disorders, Capital Medical University, Beijing,100069, China. Electronic address: [email protected].
  • 2 Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, 45267, USA; Institute of Disease Control and Prevention, Chinese Academy of Military Medical Sciences, Beijing, 100071, China.
  • 3 Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
  • 4 Institute of Disease Control and Prevention, Chinese Academy of Military Medical Sciences, Beijing, 100071, China.
  • 5 Department of Neurobiology, Beijing Key Laboratory of Major Brain Disorders, Capital Medical University, Beijing,100069, China.
  • 6 Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.
  • 7 Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, 45267, USA.
  • 8 Third Institute of Oceanography, State Oceanic Administration, Xiamen, 361005, China.
  • 9 Department of Molecular and Biomedical Pharmacology, University of Kentucky College of Medicine, Lexington KY, 40536, USA.
  • 10 Department of Neurobiology, Beijing Key Laboratory of Major Brain Disorders, Capital Medical University, Beijing,100069, China. Electronic address: [email protected].
PMID: 25514493 DOI: 10.1016/j.bbagrm.2014.12.008
Abstract

Pokemon, an important proto-oncoprotein, is a transcriptional repressor that belongs to the POK (POZ and Krüppel) family. SMAD4, a key component of TGF-β pathway, plays an essential role in TGF-β-induced transcriptional responses. In this study, we show that Pokemon can interact directly with SMAD4 both in vitro and in vivo. Overexpression of Pokemon decreases TGF-β-induced transcriptional activities, whereas knockdown of Pokemon increases these activities. Interestingly, Pokemon does not affect activation of SMAD2/3, formation of Smads complex, or DNA binding activity of SMAD4. TGF-β1 treatment increases the interaction between Pokemon and SMAD4, and also enhances the recruitment of Pokemon to Smad4-DNA complex. In addition, we also find that Pokemon recruits HDAC1 to SMAD4 complex but decreases the interaction between SMAD4 and p300/CBP. Taken together, all these data suggest that Pokemon is a new partner of SMAD4 and plays a negative role in TGF-β pathway.

Keywords

Interaction; Pokemon; Smad4; TGF-β pathway.

Figures