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(申请人提供)：HERG是一种生长因子，调节生长、分化和存活。Heregin通过直接与ErbB受体结合来刺激信号通路。HERG下游的信号通路包括Ras/ERK通路和PI3K/Akt通路。Altiok等人证明，当乳腺癌细胞用hereglin处理时，BRCA1通过PI3K/AKT途径被磷酸化(Altiok等人)。BRCA1是一种受细胞周期调控的肿瘤抑制因子，在多种氨基酸上被磷酸化。据报道，响应DNA损伤的BRCA1的磷酸化改变了蛋白质的亚细胞定位状态(Ruffner，et al.1999年)。然而，生长因子诱导BRCA1的磷酸化对其亚细胞定位的影响尚未被研究。因此，本项目将检验PI3K/Akt对BRCA1的磷酸化与亚细胞定位的相关性。假说是：hereglin-beta1通过PI3K/Akt途径促进BRCA1核定位。