| GSK3-TIP60-ULK1 signaling pathway links growth factor deprivation to autophagy. | |
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MedLine Citation:
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PMID: 22539723 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Shu-Yong Lin; Terytty Yang Li; Qing Liu; Cixiong Zhang; Xiaotong Li; Yan Chen; Shi-Meng Zhang; Guili Lian; Qi Liu; Ka Ruan; Zhen Wang; Chen-Song Zhang; Kun-Yi Chien; Jiawei Wu; Qinxi Li; Jiahuai Han; Sheng-Cai Lin |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Science (New York, N.Y.) Volume: 336 ISSN: 1095-9203 ISO Abbreviation: Science Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-04-27 Completed Date: 2012-05-10 Revised Date: 2012-08-27 |
Medline Journal Info:
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Nlm Unique ID: 0404511 Medline TA: Science Country: United States |
Other Details:
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Languages: eng Pagination: 477-81 Citation Subset: IM |
Affiliation:
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State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Fujian, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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 |
| Chemical | |
Reg. No./Substance:
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0/Culture Media; 0/Culture Media, Serum-Free; 0/Intercellular Signaling Peptides and Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/Trans-Activators; 50-99-7/Glucose; EC 2.3.1.-/KAT5 protein, human; EC 2.3.1.-/Tip60 protein, mouse; EC 2.3.1.48/Histone Acetyltransferases; EC 2.7.1.-/ULK1 protein, mouse; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/ULK1 protein, human; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.26/Glycogen Synthase Kinase 3; EC 2.7.11.26/glycogen synthase kinase 3 alpha |
| Comments/Corrections | |
Erratum In:
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Science. 2012 Aug 17;337(6096):799 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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