Identification of XIAP as a critical regulator of Wnt signaling

Identification of XIAP as a critical regulator of Wnt signaling

beta-catenin accumulates in the nucleus and binds
to the transcription factor, TCF/Lef, to activate Wnt target gene
transcription. In order for beta-catenin to bind TCF/Lef, however, the
transcriptional corepressor Groucho (Gro)/TLE, which is bound to TCF/Lef,
must be displaced. Work by Hanson et al. shows that X-linked Inhibitor of
Apoptosis (XIAP), an E3 ubiquitin ligase, is also recruited to TCF/Lef upon
Wnt signaling. XIAP ubiquitylates Groucho/TLE, thereby decreasing its
affinity for TCF/Lef and allowing for unfettered access of beta-catenin to
TCF/Lef. The figure illustrates a safety lock cover (Gro/TLE) that is used
to prevent accidental/unauthorized activation of a critical process (Wnt
signaling). Unlocking and removal of the cover (via ubiquitylation by XIAP)
allows the switch (TCF/Lef) to be activated (by beta-catenin).

The artist is
Wolfgang Wozniak, Creative Director of wolf@wolfgame.com