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