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
  • 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.