Increased interaction between DJ-1 and the Mi-2/ nucleosome remodelling and deacetylase complex during cellular stress.
DJ-1 was originally identified to be an oncogenic product, but has later been shown to be highly multifunctional. DJ-1 plays a role in oxidative stress response and transcriptional regulation, and loss of its function leads to an early onset of Parkinsonism. To further understand the mechanisms behind DJ-1's role in ... cell survival and death, we investigated alternations in endogenous DJ-1 protein-protein interaction in apoptotic cells exposed to the phosphatase inhibitor okadaic acid. By combining cellular stable isotopic labelling of amino acids in cell culture, sub-cellular fractionation, co-immunoprecipitation, and MS, we identified a novel group of DJ-1 interaction partners that increased their association to DJ-1 in okadaic acid-exposed cells. These proteins were integral components of the Mi-2/nucleosome remodelling and deacetylase (NuRD) complex. Knockdown of DJ-1 and MTA2, a core component of the NuRD complex, had a similar and pro-apoptotic effect on the transcriptional- and p53-dependent cell death induced by daunorubicin. On the other hand, MTA2 knockdown had no significant effect on the progression of p53-independent okadaic acid-induced apoptosis. Our data suggest that the increased DJ-1/NuRD interaction is a general anti-stress response regulated by okadaic acid-induced modifications of DJ-1. The observed interaction between DJ-1 and the NuRD complex may give new clues to how DJ-1 can protect cells from p53-dependent cell death.
Mesh Terms:
Apoptosis, Cell Line, Tumor, Daunorubicin, Down-Regulation, Histone Deacetylase 1, Histone Deacetylases, Humans, Intracellular Signaling Peptides and Proteins, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Okadaic Acid, Oncogene Proteins, Protein Interaction Mapping, Repressor Proteins, Reproducibility of Results, Retinoblastoma-Binding Protein 4, Stress, Physiological, Tumor Suppressor Protein p53
Apoptosis, Cell Line, Tumor, Daunorubicin, Down-Regulation, Histone Deacetylase 1, Histone Deacetylases, Humans, Intracellular Signaling Peptides and Proteins, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Okadaic Acid, Oncogene Proteins, Protein Interaction Mapping, Repressor Proteins, Reproducibility of Results, Retinoblastoma-Binding Protein 4, Stress, Physiological, Tumor Suppressor Protein p53
Proteomics
Date: Apr. 01, 2010
PubMed ID: 20127688
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