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 p85α-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.