XIAP monoubiquinates TLE

Stable Identifier
Reaction [transition]
Homo sapiens
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XIAP has been shown to ubiquitinate all human isoforms of TLE in vitro, likely in the conserved Q domain. Ubiquitination does not appear to affect the stability, localization or tetramerization of TLE; rather ubiquitination affects the interaction with TCF/LEF. Ubiquitinated TLE3 is not able to bind TCF7L2 (TCF4) in vitro and addition of XIAP to TLE3-TCF7L2 complexes promotes the dissociation of TLE from TCF7L2. Although XIAP ubiquitinates TLE in a constitutive manner, XIAP only co-immunoprecipitates with TCF7L2 upon activation of the WNT signalling pathway. These data support a model where XIAP regulates the interaction between TLE and TCF/LEF by limiting the pool of free nuclear TLE that is available for binding, and by potentially disrupting existing repression complexes at WNT-responsive promoters. By disrupting the interaction between TLE and TCF/LEF, XIAP may facilitate the recruitment of beta-catenin and the establishment of an activation complex at WNT-responsive promoters (Hanson et al, 2012)

Literature References
PubMed ID Title Journal Year
22304967 XIAP monoubiquitylates Groucho/TLE to promote canonical Wnt signaling

Beauchamp, RD, Freeman, TJ, Wallace, HA, Hanson, AJ, Lee, E, Lee, LA

Mol. Cell 2012
Catalyst Activity

ubiquitin protein ligase activity of TLE:XIAP [nucleoplasm]

Orthologous Events
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