Heregulin Beta 1 Enhances Nuclear Localization of BRCA1

Meharry Medical College, Nashville TN

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Abstract

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.