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 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.

DJ-1 Modulates Nuclear Erythroid 2–Related Factor-2–Mediated Protection in Human Primary Alveolar Type II Cells in Smokers

“…Lower DJ-1 levels were also observed in lung tissue obtained from patients with chronic obstructive pulmonary disease compared with that from control smokers (11). Moreover, it was previously reported that DJ-1 can protect cells from cell death in vitro (41). In our next approach, we wanted to determine the role of Nrf2 in ATII cell injury by CS.…”

Nuclear translocation of DJ-1 during oxidative stress-induced neuronal cell death

“…Deacetylation of p53 is mediated by an HDAC1-containing complex that includes Mi-2/ nucleosome remodeling and deacetylase (NuRD) complex [71]. Opsahl et al [72] reported that DJ-1 is a core component of the NuRD complex. They suggested that downregulation of DJ-1 facilitates p53-dependent cell death in response to apoptotic stimuli.…”

Identification of Dynamic Changes in Proteins Associated with the Cellular Cytoskeleton after Exposure to Okadaic Acid

“…Even though cytoskeletal proteins do not directly interact with lipid membranes, they interact with proteins that associate with rafts of the inner leaflet of the plasma membrane [23,24]. Isolating the lipid rafts from toxin-exposed cells, therefore, appeared as an efficient way to enrich for proteins with key functions in regulating the observed cytoskeletal reorganization and disruption of cell-cell interaction that occur in cells exposed to PP-inhibitory toxins.…”