AMPK regulates autophagy by phosphorylating BECN1 at threonine 388.

Macroautophagy/autophagy is a conserved catabolic process that recycles cytoplasmic material during low energy conditions. BECN1/Beclin1 (Beclin 1, autophagy related) is an essential protein for function of the class 3 phosphatidylinositol 3-kinase (PtdIns3K) complexes that play a key role in autophagy nucleation and elongation. Here, we show that AMP-activated protein kinase ...
(AMPK) regulates autophagy by phosphorylating BECN1 at Thr388. Phosphorylation of BECN1 is required for autophagy upon glucose withdrawal. BECN1(T388A), a phosphorylation defective mutant, suppresses autophagy through decreasing the interaction between PIK3C3 (phosphatidylinositol 3-kinase catalytic subunit type 3) and ATG14 (autophagy-related 14). The BECN1(T388A) mutant has a higher affinity for BCL2 than its wild-type counterpart; the mutant is more prone to dimer formation. Conversely, a BECN1 phosphorylation mimic mutant, T388D, has stronger binding to PIK3C3 and ATG14, and promotes higher autophagy activity than the wild-type control. These findings uncover a novel mechanism of autophagy regulation.
Mesh Terms:
AMP-Activated Protein Kinases, Animals, Apoptosis Regulatory Proteins, Autophagy, Beclin-1, Catalysis, Class III Phosphatidylinositol 3-Kinases, Fibroblasts, Gene Expression Regulation, Glucose, HEK293 Cells, HeLa Cells, Hep G2 Cells, Humans, Membrane Proteins, Mice, Mutation, Phosphatidylinositol Phosphates, Phosphorylation, Protein Multimerization, Threonine
Autophagy
Date: Dec. 01, 2015
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