Casein kinase 1 α phosphorylates the Wnt regulator Jade-1 and modulates its activity

J Biol Chem. 2014 Sep 19;289(38):26344-56. doi: 10.1074/jbc.M114.562165. Epub 2014 Aug 6.

Abstract

Tight regulation of Wnt/β-catenin signaling is critical for vertebrate development and tissue maintenance, and deregulation can lead to a host of disease phenotypes, including developmental disorders and cancer. Proteins associated with primary cilia and centrosomes have been demonstrated to negatively regulate canonical Wnt signaling in interphase cells. The plant homeodomain zinc finger protein Jade-1 can act as an E3 ubiquitin ligase-targeting β-catenin for proteasomal degradation and concentrates at the centrosome and ciliary basal body in addition to the nucleus in interphase cells. We demonstrate that the destruction complex component casein kinase 1α (CK1α) phosphorylates Jade-1 at a conserved SLS motif and reduces the ability of Jade-1 to inhibit β-catenin signaling. Consistently, Jade-1 lacking the SLS motif is more effective than wild-type Jade-1 in reducing β-catenin-induced secondary axis formation in Xenopus laevis embryos in vivo. Interestingly, CK1α also phosphorylates β-catenin and the destruction complex component adenomatous polyposis coli at a similar SLS motif to the effect that β-catenin is targeted for degradation. The opposing effect of Jade-1 phosphorylation by CK1α suggests a novel example of the dual functions of CK1α activity to either oppose or promote canonical Wnt signaling in a context-dependent manner.

Keywords: Casein Kinase 1 α; Centrosome; Cilia; NPHP4; Phosphorylation; Wnt Signaling; β-catenin (B-catenin).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Casein Kinase Ialpha / physiology*
  • Conserved Sequence
  • Enzyme Repression
  • Gene Expression
  • HEK293 Cells
  • Homeodomain Proteins / metabolism*
  • Humans
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Processing, Post-Translational*
  • Tumor Suppressor Proteins / metabolism*
  • Wnt Signaling Pathway
  • Xenopus laevis
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, human
  • Homeodomain Proteins
  • JADE1 protein, human
  • Tumor Suppressor Proteins
  • beta Catenin
  • Casein Kinase Ialpha