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Depletion of p18/LAMTOR1 promotes cell survival via activation of p27 kip1 ‐dependent autophagy under starvation
Author(s) -
Zada Sahib,
Noh Hae Sook,
Baek Seon Mi,
Ha Ji Hye,
Hahm Jong Ryeal,
Kim Deok Ryong
Publication year - 2015
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.10497
Subject(s) - autophagy , microbiology and biotechnology , programmed cell death , starvation , pi3k/akt/mtor pathway , mapk/erk pathway , endosome , chemistry , biology , apoptosis , phosphorylation , signal transduction , intracellular , biochemistry , endocrinology
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.