ULK1 phosphorylates Ser30 of BECN1 in association with ATG14 to stimulate autophagy induction.

摘要: ULK1 (unc51-like autophagy activating kinase 1) is a serine/threonine that plays key role in regulating macroautophagy/autophagy induction response to amino acid starvation. Despite the recent progress understanding functions, molecular mechanism by which regulates of remains elusive. In this study, we determined phosphorylates Ser30 BECN1 (Beclin association with ATG14 (autophagy-related 14) but not UVRAG (UV radiation resistance associated). The phosphorylation was induced deprivation acids or treatments Torin 1 rapamycin, conditions inhibit MTORC1 (mechanistic target rapamycin complex 1), and requires ATG13 RB1CC1 (RB1 inducible coiled-coil proteins interact ULK1. Hypoxia glutamine deprivation, MTORC1, also able increase manner dependent upon ULK2. Blocking replacing alanine suppressed starvation-induced activation ATG14-containing PIK3C3/VPS34 (phosphatidylinositol 3-kinase catalytic subunit type 3) kinase, reduced flux formation phagophores autophagosomes. Ser30-to-Ala mutation did affect ULK1-mediated phosphorylations Ser15 Ser29, indicating might regulate independently those 2 sites. Taken together, these results demonstrate site whose activates PIK3C3 stimulates autophagosome starvation, hypoxia, inhibition.