BRD7, a Tumor Suppressor, Interacts with p85± and Regulates PI3K Activity
Menée in vitro, cette étude met en évidence des mécanismes par lesquels, en régulant l'activité de PI3K, le gène BRD7 exerce une fonction de suppresseur de tumeurs
Phosphoinositide 3-kinase (PI3K) activity is important for regulating cell growth, survival, and motility. We report here the identification of bromodomain-containing protein 7 (BRD7) as a p85
α-interacting protein that negatively regulates PI3K signaling. BRD7 binds to the inter-SH2 (iSH2) domain of p85 through an evolutionarily conserved region located at the C terminus of BRD7. Via this interaction, BRD7 facilitates nuclear translocation of p85α. The BRD7-dependent depletion of p85 from the cytosol impairs formation of p85/p110 complexes in the cytosol, leading to a decrease in p110 proteins and in PI3K pathway signaling. In contrast, silencing of endogenous BRD7 expression by RNAi increases the steady-state level of p110 proteins and enhances Akt phosphorylation after stimulation. These data suggest that BRD7 and p110 compete for the interaction to p85. The unbound p110 protein is unstable, leading to the attenuation of PI3K activity, which suggests how BRD7 could function as a tumor suppressor.
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BRD7 interacts with the iSH2 domain of p85α
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BRD7 induces the nuclear translocation of p85α
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The BRD7-p85αcomplex leads to a decrease in p110 proteins and in PI3K signaling
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BRD7 prevents p110 from binding p85α by recruiting p85α to the nucleus
http://linkinghub.elsevier.com/retrieve/pii/S1097276514001610