Talk of the Titans: Overview of Crosstalk between Autophagy and the Ubiquitin-proteasome System

E3 ligases attach the ubiquitin (Ub)-tag to the cellular proteins and mark them for degradation in the proteasome [1]. Since everything that is created must be destroyed, the question arises: how are E3 ligases that are apt in degrading their targets themselves degraded? Two modes of E3 ligases degradation have been proposed so far: self-catalyzed ubiquitination and/or ubiquitination by an exogenous E3 ligase [2]. Recently, we proposed a novel mode of E3 ligase regulation that is centered on the ability of autophagy machinery to degrade Really-Interesting New Gene (RING)-domain E3 ligases [3]. This commentary briefly summarizes the current understanding of E3 ligase degradation and highlights our recent study in which we demonstrated the role of autophagy-associated transmembrane protein EI24 as a bridging molecule between the UPS and autophagy by regulating the degradation of several E3 ligases with RING-domains [4].