title: Gadd34 induces autophagy through the suppression of the mTOR pathway during starvation.
abstract: Several types of cellular stress induce expression of growth arrest and DNA damage protein 34 (Gadd34). Autophagy occurs under both basal conditions and conditions of stress, such as starvation. Gadd34 and autophagy are both induced under starvation conditions. In this study we found that starvation induced the expression of Gadd34, reduced mTOR activity, and induced autophagy in wild type mice, but not Gadd34 KO mice. Gadd34 bound to and dephosphorylated pTSC2 at Thr1462. Dephosphorylation of TSC2 during the starvation time period leads to the suppression of mTOR, which is a potent inhibitor of autophagy. We concluded that starvation-induced Gadd34 suppresses mTOR and, thereby, induces autophagy.
authors: Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya University, Nagoya, Japan.
authors: Mohammad Nizam
authors: MN
authors: Uddin
authors: Sachiko
authors: S
authors: Ito
authors: Naomi
authors: N
authors: Nishio
authors: Thanasegaran
authors: T
authors: Suganya
authors: Ken-ichi
authors: K
authors: Isobe
mesh_terms: D000596:Amino Acids / Q000172:deficiency; D000818:Animals; D001343:Autophagy; D015687:Cell Hypoxia; D005215:Fasting / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D005947:Glucose / Q000172:deficiency; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D000596:Amino Acids; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; C513256:Ppp1r15a protein, mouse; D054645:Protein Phosphatase 1; D005947:Glucose