In:
Science, American Association for the Advancement of Science (AAAS), Vol. 336, No. 6080 ( 2012-04-27), p. 477-481
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.
Type of Medium:
Online Resource
ISSN:
0036-8075
,
1095-9203
DOI:
10.1126/science.1217032
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2012
detail.hit.zdb_id:
128410-1
detail.hit.zdb_id:
2066996-3
detail.hit.zdb_id:
2060783-0
SSG:
11
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