Journal article
XIAP Monoubiquitylates Groucho/TLE to Promote Canonical Wnt Signaling
Molecular cell, Vol.45(5), pp.619-628
03/09/2012
DOI: 10.1016/j.molcel.2011.12.032
PMCID: PMC3299836
PMID: 22304967
Abstract
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 beta-catenin-TCF/Lef complex assembly and initiation of a Wnt-specific transcriptional program.
Details
- Title: Subtitle
- XIAP Monoubiquitylates Groucho/TLE to Promote Canonical Wnt Signaling
- Creators
- Alison J. Hanson - Vanderbilt UniversityHeather A. Wallace - Vanderbilt UniversityTanner J. Freeman - Vanderbilt UniversityR. Daniel Beauchamp - Vanderbilt UniversityLaura A. Lee - Vanderbilt UniversityEthan Lee - Vanderbilt University
- Resource Type
- Journal article
- Publication Details
- Molecular cell, Vol.45(5), pp.619-628
- DOI
- 10.1016/j.molcel.2011.12.032
- PMID
- 22304967
- PMCID
- PMC3299836
- NLM abbreviation
- Mol Cell
- ISSN
- 1097-2765
- eISSN
- 1097-4164
- Publisher
- Elsevier
- Number of pages
- 10
- Grant note
- RSG0512601; IRG5800946 / ACS; American Cancer Society P50CA95103 / NCI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R01 GM081635; 3R01GM816353S1; 5T32GM007347; 5F30ES016504; 5T32CA11992504 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 03/09/2012
- Academic Unit
- Psychiatry
- Record Identifier
- 9984822991802771
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