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Increased interaction between DJ‐1 and the Mi‐2/ nucleosome remodelling and deacetylase complex during cellular stress
Author(s) -
Opsahl Jill A.,
Hjørnevik Linda V.,
Bull Vibeke H.,
Fismen Lise,
Frøyset Ann K.,
Gromyko Darina,
Solstad Therese,
Fladmark Kari Espolin
Publication year - 2010
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200900586
Subject(s) - okadaic acid , microbiology and biotechnology , biology , programmed cell death , apoptosis , gene knockdown , immunoprecipitation , protein phosphatase 2 , phosphatase , proximity ligation assay , cell culture , biochemistry , genetics , phosphorylation , receptor
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.