Acetylated hsp70 and KAP1-mediated Vps34 SUMOylation is required for autophagosome creation in autophagy

摘要: Autophagy is a stress-induced catabolic process in which cytoplasmic components, sequestered double-membrane autophagic vesicles (AVs) or autophagosomes, are delivered to lysosomes for degradation and recycling [Kroemer G, Marino Levine B (2010) Mol Cell 40(2):280–293]. Activity of the class III phosphatidylinositol-3-OH-kinase (PI3K) vacuolar protein-sorting (Vps) 34, bound coiled-coil moesin-like B-cell lymphoma 2 (Bcl-2)–interacting protein Beclin-1, required phosphoinositide generation, essential AV formation autophagy [Cuervo AM Nat Biol 12(8):735–737]. However, how autophagy-inducing stress regulates Vps34 activity has not been fully elucidated. Our findings demonstrate that increases intracellular levels acetylated inducible heat shock (hsp) 70, binds Beclin-1–Vps34 complex. Acetylated hsp70 also recruits E3 ligase SUMOylation, KRAB–ZFP-associated 1 (KAP1), inducing Lys840 SUMOylation increasing Beclin 1. Knockdown abolished complex formation, as well inhibited KAP1 binding formation. Notably, due histone deacetylase inhibitor treatment induced wild-type but hsp70.1/3 knockout mouse embryonic fibroblasts MEFs. These highlight regulatory mechanism activity, involves KAP1-dependent