DJ-1, a cancer and Parkinson’s disease associated protein, regulates autophagy through JNK pathway in cancer cells

Ren, Haigang; Fu, Kai; Mu, Chenchen; Li, Bin; Wang, Dan; Wang, Guanghui

doi:10.1016/j.canlet.2010.05.001

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Volume 297, Issue 1 , Pages 101-108, 1 November 2010

DJ-1, a cancer and Parkinson’s disease associated protein, regulates autophagy through JNK pathway in cancer cells

Haigang Ren
- Laboratory of Molecular Neuropathology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science & Technology of China, Hefei, Anhui 230027, People’s Republic of China
- School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan 621010, People’s Republic of China
Kai Fu
- Laboratory of Molecular Neuropathology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science & Technology of China, Hefei, Anhui 230027, People’s Republic of China
Chenchen Mu
- Laboratory of Molecular Neuropathology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science & Technology of China, Hefei, Anhui 230027, People’s Republic of China
Bin Li
- Laboratory of Molecular Neuropathology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science & Technology of China, Hefei, Anhui 230027, People’s Republic of China
Dan Wang
- School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan 621010, People’s Republic of China
Guanghui Wang
- Laboratory of Molecular Neuropathology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science & Technology of China, Hefei, Anhui 230027, People’s Republic of China
- Corresponding author. Address: Department of Neurobiology, School of Life Sciences, University of Science and Technology of China, 433 Huangshan Road, Hefei, Anhui 230027, People’s Republic of China. Tel./fax: +86 551 3607058.

Received 5 February 2010; received in revised form 30 March 2010; accepted 4 May 2010. published online 01 June 2010.

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.

Abbreviations: ANOVA, analysis of variance, Atg, autophagy-related protein, EGFP, enhanced green fluorescent proteins, ERK, extracellular signal-regulated kinase, HBSS, Hanks’ balanced salt solution, HRP, horseradish peroxidase, JNK, c-Jun NH2-terminal kinase, MDC, Monodansylcadaverine, MEF, mouse embryonic fibroblast, PBS, phosphate buffer solution, RT-PCR, reverse transcription PCR, MPP+, 1-methyl-4-phenylpyridinium, PARP, Poly ADP ribose polymerase