Publication Date:
2012-04-28
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, Shu-Yong -- Li, Terytty Yang -- Liu, Qing -- Zhang, Cixiong -- Li, Xiaotong -- Chen, Yan -- Zhang, Shi-Meng -- Lian, Guili -- Liu, Qi -- Ruan, Ka -- Wang, Zhen -- Zhang, Chen-Song -- Chien, Kun-Yi -- Wu, Jiawei -- Li, Qinxi -- Han, Jiahuai -- Lin, Sheng-Cai -- New York, N.Y. -- Science. 2012 Apr 27;336(6080):477-81. doi: 10.1126/science.1217032.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Fujian, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22539723" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
*Autophagy
;
Cell Line
;
Cell Line, Tumor
;
Culture Media
;
Culture Media, Serum-Free
;
Glucose/metabolism
;
Glycogen Synthase Kinase 3/genetics/*metabolism
;
HEK293 Cells
;
Histone Acetyltransferases/genetics/*metabolism
;
Humans
;
Intercellular Signaling Peptides and Proteins/metabolism
;
Intracellular Signaling Peptides and Proteins/genetics/*metabolism
;
Mice
;
Phosphorylation
;
Protein-Serine-Threonine Kinases/genetics/*metabolism
;
Rats
;
*Signal Transduction
;
Trans-Activators/genetics/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
