title: Depletion of p18/LAMTOR1 promotes cell survival via activation of p27(kip1) -dependent autophagy under starvation.
abstract: The MAPK and mTOR signal pathways in endosomes or lysosomes play a crucial role in cell survival and death. They are also closely associated with autophagy, a catabolic process highly regulated under various cellular stress or nutrient deprivation. Recently we have isolated a protein, named p18/LAMTOR1, that specifically regulates the ERK or mTOR pathway in lysosomes. p18/LAMTOR1 also interacts with p27(kip1) . Here we examined how p18/LAMTOR1 plays a role in autophagy under nutrient deprivation. The p18(+/+) MEF cells were more susceptible to cell death under starvation or in the presence of AICAR in comparison with p18(-/-) MEF cells. Cleavage of caspase-3 was increased in p18(+/+) MEF cells under starvation, and phosphorylation at the threonine 198 of p27(kip1) was highly elevated in starved p18(-/-) MEF cells. Furthermore, LC3-II formation and other autophagy-associated proteins were largely increased in p18-deficient cells, and suppression of p27(kip1) expression in p18(-/-) MEF cells mitigated starvation-induced cell death. These data suggest that ablation of p18/LAMTOR1 suppresses starvation-induced cell death by stimulating autophagy through modulation of p27(kip1) activity.
authors.affiliation: Department of Biochemistry and Convergence Medical Sciences, Gyeongsang National University School of Medicine, JinJu, Republic of Korea.
authors.forename: Sahib
authors.initials: S
authors.lastname: Zada
authors.affiliation: Department of Biochemistry and Convergence Medical Sciences, Gyeongsang National University School of Medicine, JinJu, Republic of Korea.|Institute of Health Sciences, Gyeongsang National University School of Medicine, JinJu, Republic of Korea.
authors.forename: Hae Sook
authors.initials: HS
authors.lastname: Noh
authors.affiliation: Department of Biochemistry and Convergence Medical Sciences, Gyeongsang National University School of Medicine, JinJu, Republic of Korea.
authors.forename: Seon Mi
authors.initials: SM
authors.lastname: Baek
authors.affiliation: Department of Biochemistry and Convergence Medical Sciences, Gyeongsang National University School of Medicine, JinJu, Republic of Korea.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Ha
authors.affiliation: Institute of Health Sciences, Gyeongsang National University School of Medicine, JinJu, Republic of Korea.|Internal Medicine, Gyeongsang National University School of Medicine, JinJu, Republic of Korea.
authors.forename: Jong Ryeal
authors.initials: JR
authors.lastname: Hahm
authors.affiliation: Department of Biochemistry and Convergence Medical Sciences, Gyeongsang National University School of Medicine, JinJu, Republic of Korea.|Institute of Health Sciences, Gyeongsang National University School of Medicine, JinJu, Republic of Korea.
authors.forename: Deok Ryong
authors.initials: DR
authors.lastname: Kim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D002352:Carrier Proteins / Q000378:metabolism*; D002470:Cell Survival; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008247:Lysosomes / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D015398:Signal Transduction; D013217:Starvation / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C436291:CDKN1B protein, human; D002352:Carrier Proteins; C493961:Cdkn1b protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; C544374:LAMTOR1 protein, human; C571152:late endosome-lysosome membrane adaptor p18, mouse; D050760:Cyclin-Dependent Kinase Inhibitor p27; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases
keywords: MAPK; autophagy; mTORC1; p18/LAMTOR1; p27kip1; starvation-induced cell death