The caspase 6 derived N-terminal fragment of DJ-1 promotes apoptosis via increased ROS production.

Cell Death and Differentiation
G RobertP Auberger

Abstract

In pathological conditions, the amount of DJ-1 determines whether a cell can survive or engage a cell death program. This is exemplified in epithelial cancers, in which DJ-1 expression is increased, while autosomal recessive early onset Parkinson's disease mutations of DJ-1 generally lead to decreased stability and expression of the protein. We have shown previously that DJ-1 is cleaved by caspase-6 during induction of apoptosis. We demonstrate here that the N-terminal cleaved fragment of DJ-1 (DJ-1 Nt) is specifically expressed in the nucleus and promotes apoptosis in SH-SY5Y neuroblastoma cell lines. In addition, overexpression of DJ-1 Nt in different cell lines leads to a loss of clonogenic potential and sensitizes to staurosporin and 1-methyl-4-phenylpyridinium (MPP+)-mediated caspase activation and apoptosis. Importantly, inhibition of endogenous DJ-1 expression with sh-RNA or DJ-1 deficiency mimics the effect of DJ-1 Nt on cell growth and apoptosis. Moreover, overexpression of DJ-1 Nt increases reactive oxygen species (ROS) production, and sensitizes to MPP+-mediated apoptosis and DJ-1 oxidation. Finally, specific exclusion of DJ-1 Nt from the nucleus abrogates its pro-apoptotic effect. Taken together, our findings identi...Continue Reading

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Citations

Nov 30, 2013·Pharmacology & Therapeutics·Frédéric Checler, Cristine Alves da Costa
Aug 24, 2013·Journal of Neuropathology and Experimental Neurology·Jasmine RamcharitarAndrea C Leblanc
Oct 11, 2015·Free Radical Biology & Medicine·Lu ZhangCanhua Huang
Mar 24, 2016·Proceedings of the National Academy of Sciences of the United States of America·Olivier JulienJames A Wells
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May 10, 2017·International Journal of Molecular Sciences·Sandeep Vasant More, Dong-Kug Choi
Apr 6, 2018·Molecular Biology Reports·Walid S HabashySamuel E Aggrey
Nov 14, 2018·The Journal of Biological Chemistry·Derek J MacPhersonJeanne A Hardy
Dec 17, 2014·Oncotarget·Ivano AmelioAlessandro Rufini
Jan 24, 2021·Molecular Neurobiology·Hong-Qiu ZhangJian-Hong Zhu

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