WTIP interacts with ASXL2 and blocks ASXL2-mediated activation of retinoic acid signaling

Biochem Biophys Res Commun. 2014 Aug 15;451(1):101-6. doi: 10.1016/j.bbrc.2014.07.080. Epub 2014 Jul 24.

Abstract

The Asx-like (ASXL) family proteins are chromatin factors that play dual roles in transcriptional activation and repression. ASXL2 is highly expressed in the heart and is required for proper heart development and function. Here, we identify a novel ASXL2-binding partner, the LIM domain-containing protein WTIP. Genetic and biochemical assays show a direct interaction between ASXL2 and WTIP. In HeLa cells, ASXL2 enhances retinoic acid-dependent luciferase activity, while WTIP represses it. Furthermore, WTIP blocks ASXL2's stimulatory effect on transcription. In addition, we found that ASXL2 and WTIP are expressed in mouse embryonic epicardial cells, a tissue that is regulated by retinoic acid signaling. Together, these results implicate ASXL2 and WTIP in regulation of retinoic acid signaling during heart development.

Keywords: ASXL2; Epicardium; Heart development; Retinoic acid signaling; WTIP.

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Co-Repressor Proteins
  • Cytoskeletal Proteins
  • HeLa Cells / drug effects
  • HeLa Cells / metabolism
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • Mice
  • Pericardium / cytology
  • Pericardium / metabolism
  • Protein Structure, Tertiary
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Response Elements
  • Signal Transduction
  • Tretinoin / metabolism*
  • Tretinoin / pharmacology
  • Two-Hybrid System Techniques

Substances

  • ASXL2 protein, human
  • ASXL2 protein, mouse
  • Carrier Proteins
  • Co-Repressor Proteins
  • Cytoskeletal Proteins
  • Repressor Proteins
  • WTIP protein, human
  • Wtip protein, mouse
  • Tretinoin
  • Luciferases