Abstract

In metazoans, cells depend on extracellular growth factors for energy homeostasis. We found that glycogen synthase kinase-3 (GSK3), when deinhibited by default in cells deprived of growth factors, activates acetyltransferase TIP60 through phosphorylating TIP60-Ser(86), which directly acetylates and stimulates the protein kinase ULK1, which is required for autophagy. Cells engineered to express TIP60(S86A) that cannot be phosphorylated by GSK3 could not undergo serum deprivation-induced autophagy. An acetylation-defective mutant of ULK1 failed to rescue autophagy in ULK1(-/-) mouse embryonic fibroblasts. Cells used signaling from GSK3 to TIP60 and ULK1 to regulate autophagy when deprived of serum but not glucose. These findings uncover an activating pathway that integrates protein phosphorylation and acetylation to connect growth factor deprivation to autophagy.

Links

Publisher Full Text

Authors

Lin SY, Li TY, Liu Q, Zhang C, Li X, Chen Y, Zhang SM, Lian G, Liu Q, Ruan K, Wang Z, Zhang CS, Chien KY, Wu J, Li Q, Han J, Lin SC

Institution

State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Fujian, China.

Source

Science (New York, N.Y.) 336:6080 2012 Apr 27 pg 477-81

MeSH

Animals
Autophagy
Cell Line
Cell Line, Tumor
Culture Media
Culture Media, Serum-Free
Glucose
Glycogen Synthase Kinase 3
HEK293 Cells
Histone Acetyltransferases
Humans
Intercellular Signaling Peptides and Proteins
Intracellular Signaling Peptides and Proteins
Mice
Phosphorylation
Protein-Serine-Threonine Kinases
Rats
Signal Transduction
Trans-Activators

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22539723