Ubiquilins accelerate autophagosome maturation and promote cell survival during nutrient starvation.

摘要

Ubiquilins (UBQLN), a family of adaptor proteins with partial homology with ubiquitin, are proposed to facilitate proteasomal degradation of ubiquitinated substrates. We now demonstrate a novel role for UBQLN in promoting autophagosome maturation during nutrient deprivation. Ectopic expression of UBQLN protects cells against starvation-induced cell death, while depletion renders cells more susceptible. This protective function requires the essential autophagy regulators, Atg5 and Atg7. The ubiquitin-associated (UBA) domain of UBQLN is required for its association with autophagosomes as well as for its prosurvival functions.Remarkably, during starvation-induced autophagy, UBQLN promotes the fusion of early autophagosomes with lysosomes.Overall, this work illustrates an important function for UBQLN in cell survival during nutrient starvation, which requires a newly recognized function for UBQLN in autophagosome maturation.