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首页> 外文期刊>Molecular and Cellular Biology >SPBP Is a Phosphoserine-Specific Repressor of Estrogen Receptor α
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SPBP Is a Phosphoserine-Specific Repressor of Estrogen Receptor α

机译：SPBP是雌激素受体α的磷酸丝氨酸特异性阻遏物

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Multiple signaling pathways stimulate the activity of estrogen receptor α (ERα) by direct phosphorylation within its N-terminal activation function 1 (AF1). How phosphorylation affects AF1 activity remains poorly understood. We performed a phage display screen for human proteins that are exclusively recruited to the phosphorylated form of AF1 and found the stromelysin-1 platelet-derived growth factor-responsive element-binding protein (SPBP). In a purified system, SPBP bound only the in vitro-phosphorylated form of the ERα AF1 or the phosphoserine mimic S118E, and the interaction domain could be mapped to a 42-amino-acid fragment of SPBP. In cells, SPBP preferentially interacted with liganded and phosphorylated ERα. Functionally, SPBP behaved as a repressor of activated ERα, which extends its previously demonstrated roles as a DNA binding transactivation factor and coactivator of other transcription factors. By targeting the phosphorylated form of AF1, SPBP may contribute to attenuating and fine-tuning ERα activity. A functional consequence is that SPBP inhibits the proliferation of ERα-dependent but not ERα-independent breast cancer cell lines, mirroring a reported negative correlation with the ERα status of breast tumors.
机译：多种信号通路通过其N末端激活功能1（AF1）内的直接磷酸化刺激雌激素受体α（ERα）的活性。磷酸化如何影响AF1活性仍然知之甚少。我们对仅被募集到AF1磷酸化形式的人类蛋白质进行了噬菌体展示，发现了stromelysin-1血小板衍生的生长因子响应元件结合蛋白（SPBP）。在纯化的系统中，SPBP仅结合ERαAF1的体外磷酸化形式或磷酸丝氨酸模拟物S118E，并且相互作用域可以定位到SPBP的42个氨基酸片段上。在细胞中，SPBP优先与配体和磷酸化的ERα相互作用。在功能上，SPBP充当激活的ERα的阻遏物，扩展了其先前证明的作为DNA结合反式激活因子和其他转录因子的共激活因子的作用。通过靶向AF1的磷酸化形式，SPBP可能有助于减弱和微调ERα活性。功能性后果是SPBP抑制了ERα依赖性而不是ERα依赖性乳腺癌细胞系的增殖，这反映了与乳腺肿瘤的ERα状态负相关的报道。

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