Increased interaction between DJ-1 and the Mi-2/ nucleosome remodelling and deacetylase complex during cellular stress
Abstract
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 genera...Continue Reading
References
DJ-1 modulates UV-induced oxidative stress signaling through the suppression of MEKK1 and cell death
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Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis