Gene interactions and pathways from curated databases and text-mining
Mol Cell 2004, PMID: 15327769

Crystal structure of a beta-catenin/APC complex reveals a critical role for APC phosphorylation in APC function.

Xing, Yi; Clements, Wilson K; Le Trong, Isolde; Hinds, Thomas R; Stenkamp, Ronald; Kimelman, David; Xu, Wenqing

The tumor suppressor adenomatous polyposis coli (APC) plays a critical role in the turnover of cytosolic beta-catenin, the key effector of the canonical Wnt signaling pathway. APC contains seven 20 amino acid (20 aa) beta-catenin binding repeats that are required for beta-catenin turnover. We have determined the crystal structure of beta-catenin in complex with a phosphorylated APC fragment containing two 20 aa repeats. Surprisingly, one single phosphorylated 20 aa repeat, together with its flanking regions, covers the entire structural groove of beta-catenin and may thus compete for beta-catenin binding with all other beta-catenin armadillo repeat partners. Our biochemical studies show that phosphorylation of the APC 20 aa repeats increases the affinity of the repeats for beta-catenin by 300- to 500-fold and the phosphorylated 20 aa repeats prevent beta-catenin binding to Tcf. Our work suggests that the phosphorylation of the APC 20 aa repeats could be a critical switch for APC function.

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Text Mining Data

Tcf ⊣ APC: " Our biochemical studies show that phosphorylation of the APC 20 aa repeats increases the affinity of the repeats for beta-catenin by 300- to 500-fold and the phosphorylated 20 aa repeats prevent beta-catenin binding to Tcf "

beta-catenin ⊣ APC: " Our biochemical studies show that phosphorylation of the APC 20 aa repeats increases the affinity of the repeats for beta-catenin by 300- to 500-fold and the phosphorylated 20 aa repeats prevent beta-catenin binding to Tcf "

Manually curated Databases

  • IRef Bind Interaction: APC — CTNNB1
  • IRef Bind_translation Interaction: APC — CTNNB1 (x-ray crystallography)
  • IRef Biogrid Interaction: CTNNB1 — APC (direct interaction, unspecified method)
  • IRef Biogrid Interaction: CTNNB1 — APC (association, x-ray crystallography)
  • IRef Biogrid Interaction: CTNNB1 — APC (direct interaction, pull down)
  • IRef Biogrid Interaction: CTNNB1 — TCF3 (direct interaction, unspecified method)
  • IRef Hprd Interaction: APC — CTNNB1 (in vivo)
  • IRef Hprd Interaction: APC — CTNNB1 (in vitro)
  • IRef Hprd Interaction: TCF3 — CTNNB1 (in vivo)
  • IRef Intact Interaction: APC — CTNNB1 (direct interaction, x-ray crystallography)
  • Reactome Reaction: CTNNB1 → APC (direct_complex)
  • Reactome Reaction: AXIN1 → GSK3B (direct_complex)
  • Reactome Reaction: AXIN1 → CTNNB1 (direct_complex)
  • Reactome Reaction: APC → GSK3B (direct_complex)
  • Reactome Reaction: CSNK1A1 → GSK3B (direct_complex)
  • Reactome Reaction: AMER1 → GSK3B (direct_complex)
  • Reactome Reaction: CTNNB1 → GSK3B (direct_complex)
  • Reactome Reaction: AXIN1 → APC (direct_complex)
  • Reactome Reaction: CSNK1A1 → APC (direct_complex)
  • Reactome Reaction: CTNNB1 → CSNK1A1 (direct_complex)
  • Reactome Reaction: AMER1 → APC (direct_complex)
  • Reactome Reaction: AXIN1 → CSNK1A1 (direct_complex)
  • Reactome Reaction: AXIN1 → AMER1 (direct_complex)
  • Reactome Reaction: CSNK1A1 → AMER1 (direct_complex)
  • Reactome Reaction: CTNNB1 → AMER1 (direct_complex)
In total, 16 gene pairs are associated to this article in curated databases