Loss of function of DJ-1 triggered by Parkinson's disease-associated mutation is due to proteolytic resistance to caspase-6

58Citations
Citations of this article
58Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

DJ-1 was recently identified as a gene product responsible for a subset of familial Parkinson's disease (PD). The mechanisms by which mutations in DJ-1 alter its function and account for PD-related pathology remained largely unknown. We show that DJ-1 is processed by caspase-6 and that the caspase-6-derived C-terminal fragment of DJ-1 fully accounts for associated p53-dependent cell death. In line with the above data, we show that a recently described early-onset PD-associated mutation (D149A) renders DJ-1 resistant to caspase-6 proteolysis and abolishes its protective phenotype. Unlike the D149A mutation, the L166P mutation that prevents DJ-1 dimerization does not impair its proteolysis by caspase-6 although it also abolishes DJ-1 antiapoptotic function. Therefore, we show here that DJ-1 loss of function could be due to impaired caspase-6 proteolysis and we document the fact that various DJ-1 mutations could lead to PD pathology through distinct molecular mechanisms. © 2010 Macmillan Publishers Limited All rights reserved.

Cite

CITATION STYLE

APA

Giaime, E., Sunyach, C., Druon, C., Scarzello, S., Robert, G., Grosso, S., … Da Costa, C. A. (2010). Loss of function of DJ-1 triggered by Parkinson’s disease-associated mutation is due to proteolytic resistance to caspase-6. Cell Death and Differentiation, 17(1), 158–169. https://doi.org/10.1038/cdd.2009.116

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free