Figure 1.

Crosstalk between the UPS and autophagy. The proposed molecular circuit in which USP14 is a common denominator of the UPS and autophagy in the compensatory negative feedback connection. When USP14 is inhibited, activated proteasomes result in the degradation of UVRAG, which subsequently leads to a reduction in autophagic flux. Inversely, when cellular autophagy is induced via nutrient deprivation, proteasomal activity is reduced and levels of UPS substrates are elevated. The underlying mechanism mediating proteasome inactivation upon autophagy induction needs to be identified.