The Wnt signaling antagonist XXXX accelerates Dishevelled2 degradation via promoting its ubiquitination and aggregates-induced autophagy.

@entity13054 @entity42627 @entity18677 @entity10407 @entity18678 @entity8783 @entity12226 @entity280 @entity26814
UNASSIGNED: Autophagy is a regulated process that sequesters and transports cytoplasmic materials such as protein aggregates via autophagosomes to lysosomes for degradation. @entity13054 ( @entity13054 ), an interacting protein of @entity18677 ( @entity18677 ), antagonizes Wnt signaling by promoting @entity18677 degradation via lysosomes. However, the mechanism is unclear. Here, we show that @entity13054 promotes the @entity280 suppressor ( @entity12226 )-mediated ubiquitination of @entity18678 and its autophagic degradation. Knockdown of @entity13054 decreases the interaction between @entity18678 and @entity12226 , resulting in reduced ubiquitination of @entity18678 . @entity13054 -mediated autophagic degradation of @entity18678 depends on @entity18678 aggregation. Moreover, the aggregate-prone proteins @entity18678 , @entity10407 and the hungtingtin mutant Htt103Q promote autophagy in a @entity13054 -dependent manner. These protein aggregates enhance the @entity8783 - @entity26814 interaction and @entity42627 puncta formation, indicating that aggregated proteins stimulate autophagy initiation. Ubiquitination is not essential for the aggregates-induced autophagy initiation as inhibition of the ubiquitin-activation E1 enzyme activity did not block the aggregates-induced @entity42627 puncta formation. Our findings suggest that @entity13054 promotes the ubiquitination of @entity18678 by @entity12226 and mediates the protein aggregates-elicited autophagy initiation.
