Control of beta-catenin stability: Reconstitution of the cytoplasmic stepsof the wnt pathway in Xenopus egg extracts

Regulation of beta-catenin degradation by intracellular components of the w nt pathway was reconstituted in cytoplasmic extracts of Xenopus eggs and em bryos. The ubiquitin-dependent beta-catenin degradation in extracts display s a biochemical requirement for axin, GSK3, and APC. Axin dramatically acce lerates while dishevelled inhibits beta-catenin turnover. Through another d omain, dishevelled recruits GBP/Frat1 to the APC-axin-GSK3 complex. Our res ults confirm and extend models in which inhibition of GSK3 has two synergis tic effects: (1) reduction of APC phosphorylation and loss of affinity for beta-catenin and (2) reduction of beta-catenin phosphorylation and conseque nt loss of its affinity for the SCF ubiquitin ligase complex. Dishevelled t hus stabilizes beta-catenin, which can dissociate from the APC/axin complex and participate in transcriptional activation.