Reactome | XIAP binds TLE

XIAP binds TLE

Stable Identifier

R-HSA-3322431

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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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

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
14685266	A novel role for XIAP in copper homeostasis through regulation of MURR1 Klomp, LW, Duckett, CS, Wilkinson, JC, Nabel, GJ, van De Sluis, B, Ganesh, L, Brewer, GJ, Dick, RD, Burstein, E, Wijmenga, C	EMBO J.	2004
19590513	XIAP as a ubiquitin ligase in cellular signaling Duckett, CS, Galbán, S	Cell Death Differ.	2010