BRD7 是一种肿瘤抑制因子，与 p85α 相互作用并调节 PI3K 活性。
BRD7, a tumor suppressor, interacts with p85α and regulates PI3K activity.
机构信息
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA; Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
出版信息
Mol Cell. 2014 Apr 10;54(1):193-202. doi: 10.1016/j.molcel.2014.02.016. Epub 2014 Mar 20.
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.
磷酸肌醇 3-激酶（PI3K）的活性对于调节细胞生长、存活和运动至关重要。我们在这里报告了溴结构域蛋白 7（BRD7）作为一个 p85α 相互作用蛋白的鉴定，它负调控 PI3K 信号。BRD7 通过位于 BRD7 C 端的进化上保守区域与 p85 的间-SH2（iSH2）结构域结合。通过这种相互作用，BRD7 促进了 p85α 的核易位。BRD7 依赖性将 p85 从细胞质中耗竭会损害细胞质中 p85/p110 复合物的形成，导致 p110 蛋白减少和 PI3K 途径信号转导减少。相比之下，通过 RNAi 沉默内源性 BRD7 表达会增加 p110 蛋白的稳态水平，并增强刺激后的 Akt 磷酸化。这些数据表明 BRD7 和 p110 竞争与 p85 的相互作用。未结合的 p110 蛋白不稳定，导致 PI3K 活性减弱，这表明 BRD7 如何作为肿瘤抑制因子发挥作用。
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