DJ-1, a cancer and Parkinson's disease associated protein, regulates autophagy through JNK pathway in cancer cells.
Autophagy mediates cellular self-digestion to degrade cytoplasmic proteins and organelles and plays important roles in tumorigenesis. DJ-1 is an oncogene product in association with cancers and tumorigenesis. In this study, we show that knockdown of DJ-1 induces autophagy through activating JNK pathway to promote Beclin 1 transcription, whereas overexpression of DJ-1 inhibits these processes. Moreover, inhibition of JNK pathway by SP600125 blocks autophagy activation and p62 degradation induced by knockdown of DJ-1. Our findings suggest that DJ-1 regulates autophagy in a JNK-dependent manner. Thus, the involvement of DJ-1 in autophagy regulation may be involved in tumorigenesis.
University of Science & Technology of China, Hefei, Anhui, People's Republic of China.
Haigang
H
Ren
Kai
K
Fu
Chenchen
C
Mu
Bin
B
Li
Dan
D
Wang
Guanghui
G
Wang
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000873:Anthracenes / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D000071617:Protein Deglycase DJ-1; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D000071456:Sequestosome-1 Protein; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D000873:Anthracenes; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D015513:Oncogene Proteins; D047428:Protein Kinase Inhibitors; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1