ATG5 cancer mutations and alternative mRNA splicing reveal a conjugation switch that regulates ATG12-ATG5-ATG16L1 complex assembly and autophagy.

ABSTRACT: Autophagy is critical for maintaining cellular homeostasis during times of stress, and is thought to play important roles in both tumorigenesis and tumor cell survival. Formation of autophagosomes, which mediate delivery of cytoplasmic cargo to lysosomes, requires multiple autophagy-related (ATG) protein complexes, including the ATG12-ATG5-ATG16L1 complex. Herein, we report that a molecular ATG5 "conjugation switch", comprised of competing ATG12 and ubiquitin conjugation reactions, integrates ATG12-ATG5-ATG16L1 complex assembly with protein quality control of its otherwise highly unstable subunits. This conjugation switch is tightly regulated by ATG16L1, which binds to free ATG5 and mutually protects both proteins from ubiquitin conjugation and proteasomal degradation, thereby instead prom

SUBMITTER: Wible DJ 

PROVIDER: S-EPMC6796855 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature