PMID- 26733200
OWN - NLM
STAT- MEDLINE
DCOM- 20160801
LR  - 20211203
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 291
IP  - 9
DP  - 2016 Feb 26
TI  - The Transcription Factor p8 Regulates Autophagy in Response to Palmitic Acid 
      Stress via a Mammalian Target of Rapamycin (mTOR)-independent Signaling Pathway.
PG  - 4462-72
LID - 10.1074/jbc.M115.675793 [doi]
AB  - Autophagy is an evolutionarily conserved degradative process that allows cells to 
      maintain homoeostasis in numerous physiological situations. This process also 
      functions as an essential protective response to endoplasmic reticulum (ER) 
      stress, which promotes the removal and degradation of unfolded proteins. However, 
      little is known regarding the mechanism by which autophagy is initiated and 
      regulated in response to ER stress. In this study, different types of autophagy 
      were identified in human gastric cancer MKN45 cells in response to the stress 
      induced by nutrient starvation or lipotoxicity in which the regulation of these 
      pathways is mammalian target of rapamycin (mTOR)-dependent or -independent, 
      respectively. Interestingly, we found that p8, a stress-inducible transcription 
      factor, was enhanced in MKN45 cells treated with palmitic acid to induce 
      lipotoxicity. Furthermore, an increase in autophagy was observed in MKN45 cells 
      stably overexpressing p8 using a lentivirus system, and autophagy induced by 
      palmitic acid was blocked by p8 RNAi compared with the control. Western blotting 
      analyses showed that autophagy was regulated by p8 or mTOR in response to the 
      protein kinase-like endoplasmic reticulum kinase/activating transcription factor 
      6-mediated ER stress of lipotoxicity or the parkin-mediated mitochondrial stress 
      of nutrient starvation, respectively. Furthermore, our results indicated that 
      autophagy induced by palmitic acid is mTOR-independent, but this autophagy 
      pathway was regulated by p8 via p53- and PKCalpha-mediated signaling in MKN45 cells. 
      Our findings provide insights into the role of p8 in regulating autophagy induced 
      by the lipotoxic effects of excess fat accumulation in cells.
CI  - (c) 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Jia, Sheng-Nan
AU  - Jia SN
AD  - From the College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
FAU - Lin, Cheng
AU  - Lin C
AD  - From the College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
FAU - Chen, Dian-Fu
AU  - Chen DF
AD  - From the College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
FAU - Li, An-Qi
AU  - Li AQ
AD  - From the College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
FAU - Dai, Li
AU  - Dai L
AD  - From the College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
FAU - Zhang, Li
AU  - Zhang L
AD  - From the College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
FAU - Zhao, Ling-Ling
AU  - Zhao LL
AD  - From the College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
FAU - Yang, Jin-Shu
AU  - Yang JS
AD  - From the College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
FAU - Yang, Fan
AU  - Yang F
AD  - From the College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
FAU - Yang, Wei-Jun
AU  - Yang WJ
AD  - From the College of Life Sciences, Zhejiang University, Hangzhou 310058, China 
      w_jyang@zju.edu.cn.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160105
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Sp8 protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (enhanced green fluorescent protein)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 2V16EO95H1 (Palmitic Acid)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - *Autophagy/drug effects
MH  - Cell Line, Tumor
MH  - DNA-Binding Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - *Endoplasmic Reticulum Stress/drug effects
MH  - Fatty Acids, Nonesterified/*adverse effects
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - MAP Kinase Signaling System/drug effects
MH  - Microscopy, Fluorescence
MH  - Palmitic Acid/adverse effects
MH  - Protein Kinase Inhibitors/pharmacology
MH  - RNA Interference
MH  - Recombinant Fusion Proteins/chemistry/metabolism
MH  - *Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Transcription Factors/antagonists & inhibitors/genetics/*metabolism
MH  - *Up-Regulation/drug effects
PMC - PMC4813474
OTO - NOTNLM
OT  - autophagy
OT  - lipotoxicity
OT  - mammalian target of rapamycin (mTOR)
OT  - p53
OT  - p8
OT  - protein kinase C (PKC)
EDAT- 2016/01/07 06:00
MHDA- 2016/08/02 06:00
PMCR- 2017/02/26
CRDT- 2016/01/07 06:00
PHST- 2015/07/01 00:00 [received]
PHST- 2017/02/26 00:00 [pmc-release]
PHST- 2016/01/07 06:00 [entrez]
PHST- 2016/01/07 06:00 [pubmed]
PHST- 2016/08/02 06:00 [medline]
AID - S0021-9258(20)43593-8 [pii]
AID - M115.675793 [pii]
AID - 10.1074/jbc.M115.675793 [doi]
PST - ppublish
SO  - J Biol Chem. 2016 Feb 26;291(9):4462-72. doi: 10.1074/jbc.M115.675793. Epub 2016 
      Jan 5.