Structural and functional characterization of tumor suppressors TIG3 and H-REV107

FEBS Lett. 2015 May 8;589(11):1179-86. doi: 10.1016/j.febslet.2015.04.002. Epub 2015 Apr 11.

Abstract

H-REV107-like family proteins TIG3 and H-REV107 are class II tumor suppressors. Here we report that the C-terminal domains (CTDs) of TIG3 and H-REV107 can induce HeLa cell death independently. The N-terminal domain (NTD) of TIG3 enhances the cell death inducing ability of CTD, while NTD of H-REV107 plays an inhibitory role. The solution structure of TIG3 NTD is very similar to that of H-REV107 in overall fold. However, the CTD binding regions on NTD are different between TIG3 and H-REV107, which may explain their functional difference. As a result, the flexible main loop of H-REV107, but not that of TIG3, is critical for its NTD to modulate its CTD in inducing cell death.

Keywords: H-REV107; NMR; Solution structure; TIG3; Tumor suppressor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Death / genetics
  • HeLa Cells
  • Humans
  • Phospholipases A2, Calcium-Independent / chemistry*
  • Phospholipases A2, Calcium-Independent / genetics
  • Phospholipases A2, Calcium-Independent / metabolism*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Receptors, Retinoic Acid / chemistry*
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / metabolism*
  • Structure-Activity Relationship
  • Tumor Suppressor Proteins / chemistry*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • PLAAT4 protein, human
  • Receptors, Retinoic Acid
  • Tumor Suppressor Proteins
  • PLAAT3 protein, human
  • Phospholipases A2, Calcium-Independent