Dr. Shih, Hsiu-Ming 's publons link picture

Dr. Shih, Hsiu-Ming

Research Fellow
  • 2789-9060 (Lab) (Room No: N605)
  • 2652-3520 (Office)
  • 2782-7654 (Fax)

Specialty:
  • Protein-protein Interaction & Modification
  • Cancer Cell Signaling
  • Transcriptional Control

Education and Positions:
  • Ph.D. Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota


Highlight Detail
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The role of sentrin-specific protease 2 substrate recognition in TGF-β-induced tumorigenesis

Dr. Shih, Hsiu-Ming
Scientific Reports, Jun 28, 2018

 

Abstract

Smad4, a common-mediator of Smads, plays a central role in forming complexes with receptor-phosphorylated Smads, and then transduces transforming growth factor (TGF)-β signals into the nuclei. Although many cellular factors are involved in TGF-β induced epithelial-to-mesenchymal transition (EMT) and cell migration, very little is known with the mechanism of Smad4 regulation on pro-oncogenes response by TGF-β. Herein, we demonstrate the interaction of Sentrin-specific protease 2 (SENP2) with Smad4 through SENP2 residue 363~400. The same segment is also important for desumoylation of Smad4, and able to relieve sumoylation-mediated TGF-β repression. The SENP2363~400 segment is critical for TGF-β-induced cell migration, which is correlated with SENP2363~400 deletion mutant failed to increase matrix metalloproteinase (MMP)-9 and EMT marker gene expression. Moreover, our results suggest that the interaction and desumoylation between SENP2 and Smad4 promote cell migration in triple-negative breast cancer cells. Altogether, our data show how SENP2 regulates its substrate for desumoylation, and also the role of SENP2 in TGF-β induced cancer cell migration.