Heregulin Beta 1 Enhances Nuclear Localization of BRCA1

描述（由申请人提供）： 调蛋白（HRG）是一种调节生长、分化和存活的生长因子。调蛋白通过直接结合ErbB受体刺激信号传导途径。作为调蛋白下游靶标的信号传导途径包括Ras/ERK途径和PI3K/Akt途径。Altiok等人证明，当用heregulin处理乳腺癌细胞时，BRCA 1通过PI3K/AKT途径磷酸化（Altiok等人）。BRCA1是一种细胞周期调节的肿瘤抑制因子，在多个氨基酸处磷酸化。据报道，BRCA 1的磷酸化响应DNA损伤改变了蛋白质的亚细胞定位状态（Ruffner，et al. 1999）。然而，由生长因子诱导的BRCA 1磷酸化对其亚细胞定位的影响尚未研究。因此，本项目将检测BRCA1通过PI3K/Akt磷酸化与亚细胞定位的相关性。假设：Heregulin-beta1通过PI3K/Akt途径增强BRCA1的核定位。

DESCRIPTION (provided by applicant): Heregulin (HRG) is a growth factor that regulates growth, differentiation, and survival. Heregulin stimulates signaling pathways through direct binding to the ErbB receptors. Signaling pathways that are downstream targets of heregulin include the Ras/ERK pathway, and the PI3K/Akt pathway. Altiok et al demonstrated that when breast cancer cells are treated with heregulin, BRCA1 is phosphorylated through the PI3K/AKT pathway (Altiok, et al). BRCA1 is a cell cycle-regulated tumor suppressor that is phosphorylated at multiple amino acids. It has been reported that phosphorylation of BRCA1 in response to DNA damage changes the subcellular localization state of the protein (Ruffner, et al. 1999). However, the effects of phosphorylation of BRCA1 induced by a growth factor on its subcellular localization have not been investigated. Therefore, this project will test the correlation of phosphorylation of BRCA1 by PI3K/Akt and subcellular localization. The hypothesis is: Heregulin- beta1 enhances BRCA1 nuclear localization through the PI3K/Akt pathway.