Heregulin Beta 1 Enhances Nuclear Localization of BRCA1

Heregulin Beta 1 增强 BRCA1 的核定位

• 批准号: 6691421
• 负责人: Cimona V Hinton
• 金额: $ 3.18万
• 依托单位: MEHARRY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6691421
• 关键词: MCF7 cell; brca gene; enzyme activity; enzyme inhibitors; extracellular matrix proteins; heregulin; immunocytochemistry; neuregulins; phosphatidylinositol 3 kinase; phosphorylation; predoctoral investigator; protein localization; serine threonine protein kinase; site directed mutagenesis

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.

描述（由申请人提供）：Heregulin (HRG) 是一种调节生长、分化和存活的生长因子。 Heregulin 通过直接结合 ErbB 受体来刺激信号传导通路。作为调蛋白下游靶标的信号通路包括 Ras/ERK 通路和 PI3K/Akt 通路。 Altiok 等人证明，当乳腺癌细胞用调蛋白处理时，BRCA1 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，其多个氨基酸被磷酸化。据报道，BRCA1 对 DNA 损伤的磷酸化改变了该蛋白的亚细胞定位状态 (Ruffner, et al. 1999)。然而，生长因子诱导的 BRCA1 磷酸化对其亚细胞定位的影响尚未得到研究。因此，本项目将测试PI3K/Akt磷酸化BRCA1与亚细胞定位的相关性。假设是：Heregulin-beta1 通过 PI3K/Akt 途径增强 BRCA1 核定位。