Reactome: A Curated Pathway Database

XIAP binds TLE

Stable Identifier
R-HSA-3322431
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

XIAP (X-linked inhibitor of apoptosis) has three BIR domains with known roles in the degradation of caspases and a C-terminal E3 ligase domain with both anti-apoptotic and non-apoptotic roles (Galban and Duckett, 2010; Burstein et al, 2004). The Drosophila homologue DAIP1 was recently identified in a screen in S2 cells for regulators of Wg signalling (Hanson et al, 2012). Knockdown of XIAP in HEK293 cells reduces WNT3a-induced reporter activity and expression of endogenous WNT target genes without affecting beta-catenin levels or localization. In vitro studies show that XIAP can ubiquitinate all human TLE isoforms, including the truncated isoform Amino-terminal enhancer of split (AES). TLE3 co-immunoprecipitates with XIAP from HEK293 cells in both the presence and absence of WNT signalling, consistent with a constitutive role for XIAP in TLE regulation. XIAP may act either by ubiquitinating free nuclear TLE to reduce the amount available to interact with TCF/LEFs or by ubiquitinating TLE in the context of TCF/LEF transcriptional complexes to promote its dissociation, or both. In support of the latter model, XIAP is pulled down with TCF7L2 (TCF4) in a WNT-dependent manner, and knockdown of XIAP reduces the amount of beta-catenin that co-immunoprecipitates with TCF7L2 (TCF4) upon WNT pathway activation (Hanson et al, 2012).

Literature References
Participants
Participant Of
Orthologous Events