Interference of E2-2-mediated effect in endothelial cells by FAM96B through its limited expression of E2-2

Cancer Sci. 2011 Oct;102(10):1808-14. doi: 10.1111/j.1349-7006.2011.02022.x. Epub 2011 Aug 2.

Abstract

The basic helix–loop–helix protein E2-2 is known to play a role in quiescence of endothelial cells (ECs). However, it is unclear how the activity of E2-2 is controlled in the cells. In this study, we identified FAM96B as an interaction partner of E2-2. FAM96B interfered with E2-2-mediated effects on luciferase reporter activities. Furthermore, the suppression of vascular endothelial growth factor receptor 2 promoter activity by E2-2 was rescued by the expression of FAM96B in a dose-dependent manner. Interestingly, FAM96B decreased the expression of ectopic and endogenous E2-2 proteins. Mutational analysis revealed that the middle region of FAM96B is required for the limited expression of E2-2 protein. When FAM96B was expressed in ECs, the EC migration, proliferation, and tube formation were potentiated. Taken together, these findings suggest that FAM96B acts as a regulator of E2-2 through the control of its protein expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • COS Cells
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Movement
  • Cell Proliferation
  • Cricetinae
  • Endothelial Cells / metabolism*
  • Helix-Loop-Helix Motifs
  • Humans
  • Metalloproteins
  • Mice
  • NIH 3T3 Cells
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Promoter Regions, Genetic
  • Sequence Analysis, DNA
  • Transcription Factor 7-Like 2 Protein / genetics
  • Transcription Factor 7-Like 2 Protein / metabolism*
  • Vascular Endothelial Growth Factor Receptor-2 / genetics*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • CIAO2B protein, human
  • Carrier Proteins
  • Metalloproteins
  • Nuclear Proteins
  • TCF7L2 protein, human
  • Transcription Factor 7-Like 2 Protein
  • Vascular Endothelial Growth Factor Receptor-2