Identification of ATF5-Interacting, SH3-Containing Proteins in Breast Cancer Cells

摘要

Growing evidence suggests that ATF5, a member of the ATF/CREB family of transcription factors, is a cancer-specific cell survival factor. ATF5 is highly expressed in breast carcinomas and several other types of cancer cells; interference of ATF5 function in those cells causes cell death. Surprisingly, similar interference of ATF5 function in normal or non-cancer breast cells does not affect their survival. Consistent with a required role for ATF5 in survival of cancer cells, ATF5 is down-regulated in a number of cancer cells in response to trophic withdrawal, which induces cell death of those cells. Moreover, overexpression of ATF5 blocks such death. The mechanism underlying ATF5-regulated cellular functions is unknown. The overarching goal for this research is to identify the proteins that interact with ATF5 and that impact on ATF5's cancer-specific cell survival function. The purpose of this research is to understand how ATF5 acts as a cancer-specific cell survival factor in breast cancer cells and use this information to selectively destroy breast cancer.