Unbound MEDLINE

GSK3-TIP60-ULK1 signaling pathway links growth factor deprivation to autophagy.

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.

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  • FREE 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

    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