Dishevelled-DEP domain interacting protein (DDIP) inhibits Wnt signaling by promoting TCF4 degradation and disrupting the TCF4/beta-catenin complex

Cell Signal. 2010 Nov;22(11):1753-60. doi: 10.1016/j.cellsig.2010.06.016. Epub 2010 Jul 22.

Abstract

The TCF4/beta-catenin complex, the executor of canonical Wnt/beta-catenin signaling, is regulated by a variety of factors. Among these, Dishevelled (Dvl) is a critical regulator that releases beta-catenin from degradation and stabilizes TCF4/beta-catenin complex. Here, we report that DDIP (Dishevelled-DEP domain Interacting Protein, also named as Spats1, spermatogenesis associated, serine-rich 1), a novel protein that interacts with Dvl, regulates Wnt signaling. We provide evidence that DDIP suppresses Lef-1 luciferase reporter activity stimulated by Wnt1, Dvl2 or beta-catenin, interacts with the TCF4/beta-catenin complex, and disrupts the interaction of TCF4 and beta-catenin by promoting TCF4 degradation through the proteasome pathway. Our results indicate that DDIP is a negative regulator of the canonical Wnt signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
  • Cell Line
  • Cell Proliferation
  • Dishevelled Proteins
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Phosphoproteins / metabolism
  • Signal Transduction*
  • Transcription Factor 4
  • Transcription Factors / metabolism*
  • Wnt1 Protein / antagonists & inhibitors
  • Wnt1 Protein / metabolism*
  • beta Catenin / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • DVL2 protein, human
  • Dishevelled Proteins
  • Dvl2 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • SPATS1 protein, human
  • TCF4 protein, human
  • Transcription Factor 4
  • Transcription Factors
  • WNT1 protein, human
  • Wnt1 Protein
  • beta Catenin