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.
Opsahl
Jill A
JA
Proteomic Unit (PROBE), Department of Biomedicine, University of Bergen, Bergen, Norway.
Hjørnevik
Linda V
LV
Bull
Vibeke H
VH
Fismen
Lise
L
Frøyset
Ann K
AK
Gromyko
Darina
D
Solstad
Therese
T
Fladmark
Kari Espolin
KE
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003630:Daunorubicin / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D056284:Histone Deacetylase 1 / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000378:metabolism*; D019319:Okadaic Acid / Q000494:pharmacology; D015513:Oncogene Proteins / Q000378:metabolism*; D000071617:Protein Deglycase DJ-1; D025941:Protein Interaction Mapping / Q000379:methods*; D012097:Repressor Proteins / Q000378:metabolism; D015203:Reproducibility of Results; D056505:Retinoblastoma-Binding Protein 4 / Q000378:metabolism; D013312:Stress, Physiological; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; C082637:RBBP4 protein, human; D012097:Repressor Proteins; D056505:Retinoblastoma-Binding Protein 4; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019319:Okadaic Acid; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; C120917:MTA2 protein, human; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D003630:Daunorubicin