Abstract
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.
2010 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / metabolism
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Anthracenes / pharmacology
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Apoptosis Regulatory Proteins / metabolism
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Autophagy* / drug effects
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Beclin-1
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HeLa Cells
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Humans
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
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JNK Mitogen-Activated Protein Kinases / metabolism*
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Membrane Proteins / metabolism
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Neoplasms / enzymology*
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Neoplasms / genetics
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Neoplasms / pathology
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Oncogene Proteins / genetics
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Oncogene Proteins / metabolism*
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Protein Deglycase DJ-1
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Protein Kinase Inhibitors / pharmacology
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RNA Interference
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Sequestosome-1 Protein
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Signal Transduction* / drug effects
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Transfection
Substances
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Adaptor Proteins, Signal Transducing
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Anthracenes
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Apoptosis Regulatory Proteins
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BECN1 protein, human
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Beclin-1
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Oncogene Proteins
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Protein Kinase Inhibitors
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SQSTM1 protein, human
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Sequestosome-1 Protein
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pyrazolanthrone
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JNK Mitogen-Activated Protein Kinases
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PARK7 protein, human
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Protein Deglycase DJ-1