XIAP monoubiquitylates Groucho/TLE to promote canonical Wnt signaling.

Hanson AJ, Wallace HA, Freeman TJ, Beauchamp RD, Lee LA, Lee E
Mol Cell. 2012 45 (5): 619-28

PMID: 22304967 · PMCID: PMC3299836 · DOI:10.1016/j.molcel.2011.12.032

A key event in Wnt signaling is conversion of TCF/Lef from a transcriptional repressor to an activator, yet how this switch occurs is not well understood. Here, we report an unanticipated role for X-linked inhibitor of apoptosis (XIAP) in regulating this critical Wnt signaling event that is independent of its antiapoptotic function. We identified DIAP1 as a positive regulator of Wingless signaling in a Drosophila S2 cell-based RNAi screen. XIAP, its vertebrate homolog, is similarly required for Wnt signaling in cultured mammalian cells and in Xenopus embryos, indicating evolutionary conservation of function. Upon Wnt pathway activation, XIAP is recruited to TCF/Lef where it monoubiquitylates Groucho (Gro)/TLE. This modification decreases affinity of Gro/TLE for TCF/Lef. Our data reveal a transcriptional switch involving XIAP-mediated ubiquitylation of Gro/TLE that facilitates its removal from TCF/Lef, thus allowing β-catenin-TCF/Lef complex assembly and initiation of a Wnt-specific transcriptional program.

Copyright © 2012 Elsevier Inc. All rights reserved.

MeSH Terms (17)

Animals Co-Repressor Proteins Drosophila Drosophila Proteins Embryo, Nonmammalian HEK293 Cells Humans Inhibitor of Apoptosis Proteins Models, Genetic RNA Interference Ubiquitination Wnt1 Protein Wnt Proteins Wnt Signaling Pathway X-Linked Inhibitor of Apoptosis Protein Xenopus Xenopus Proteins

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