Role of the MAPK/cJun NH2-terminal kinase signaling pathway in starvation-induced autophagy

Abstract

Autophagy is required for cellular homeostasis and can determine cell viability in response to stress. It is established that MTOR is a master regulator of starvation-induced macroautophagy/autophagy, but recent studies have also implicated an essential role for the MAPK8/cJun NH2-terminal kinase 1 signal transduction pathway. We found that MAPK8/JNK1 and MAPK9/JNK2 were not required for autophagy caused by starvation or MTOR inhibition in murine fibroblasts and epithelial cells. These data demonstrate that MAPK8/9 has no required role in starvation-induced autophagy. We conclude that the role of MAPK8/9 in autophagy may be context-dependent and more complex than previously considered. Abbreviations: AKT: thymoma viral proto-oncogene;ALB: albumin; ATG4: autophagy related 4; BCL2: B cell leukemia/lymphoma 2; BECN1: beclin 1, autophagy related; BNIP3: BCL2/adenovirus E1B interacting protein 3; CQ: chloroquine diphosphate; DMEM: Dulbecco’s modified Eagle’s medium; EDTA: ethylenediaminetetraacetic acid; EBSS: Earle’s balanced salt solution; FBS: fetal bovine serum; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; HRAS: Harvey rat sarcoma virus oncogene; IgG: Immunoglobulin G; MAPK3/ERK1: mitogen-activated protein kinase 3; MAPK8/JNK1: mitogen-activated protein kinase 8; MAPK9/JNK2: mitogen-activated protein kinase 9; MAPK10/JNK3: mitogen-activated protein kinase 10; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MEFs: mouse embryonic fibroblasts; MTOR: mechanistic target of rapamycin kinase; RPS6KB1/p70: ribosomal protein S6 kinase, polypeptide 1; PPARA: peroxisome proliferator activated receptor alpha; SEM: standard error of the mean; SQSTM1/p62: sequestosome 1; TORC1: target of rapamycin complex 1; TORC2: target of rapamycin complex 2; TRP53: transforming related protein 53; TUBA: tubulin alpha; UV: ultraviolet; WT: wild-type.