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A novel functional screen in human cells identifies MOCA as a negative regulator of Wnt signaling

Elanite Caspi1, Rina Rosin-Arbesfeld

  • 1Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.

Molecular Biology of the Cell
|August 22, 2008
PubMed

Insights

Aberrant Wnt signaling contributes to diseases like cancer. Researchers identified MOCA as a novel Wnt pathway inhibitor, which complexes with beta-catenin to suppress Wnt target genes and enhance cell adhesion.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Aberrant Wnt signal transduction is implicated in various human diseases, including cancer and neurodegenerative disorders.
  • Beta-catenin is the key effector protein in the canonical Wnt pathway, partnering with T-cell factor/lymphoid enhancer factor (TCF/LEF) to drive Wnt target gene expression.

Purpose of the Study:

  • To identify novel negative regulators of the Wnt pathway using a functional screen of a human brain cDNA library.
  • To characterize the role of the modifier of cell adhesion (MOCA) gene, identified through the screen, as a Wnt pathway inhibitor.

Main Methods:

  • A novel functional screen of a human brain cDNA library was employed to identify genes regulating Wnt signaling.
  • The interaction of MOCA with beta-catenin and its effect on Wnt target gene transcription were investigated.
  • Epistasis experiments were conducted to elucidate the mechanism of MOCA action within the Wnt pathway.

Main Results:

  • The screen identified 63 putative negative Wnt regulators, categorized into eight functional groups.
  • MOCA was identified as a novel inhibitor of Wnt/beta-catenin signaling.
  • MOCA forms a complex with beta-catenin, inhibiting Wnt target gene transcription, reducing nuclear beta-catenin, increasing membrane-bound beta-catenin, and enhancing cell-cell adhesion.

Conclusions:

  • MOCA is a novel negative regulator of Wnt signaling.
  • The screening approach provides a rapid method for isolating new Wnt pathway regulators.
  • Understanding MOCA's role may offer new therapeutic strategies for Wnt-related diseases.

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