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- W2067148897 abstract "Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FLThe activating transcription factor 5 (ATF5) is a member of the ATF/CREB family of basic zipper (bZIP) proteins. Recent reports showed that ATF5 loss-of-function causes apoptotic cell death in glioblastoma and breast cancer cells but not in non-transformed astrocytes and human breast epithelial cells. The mechanism for ATF5's cell type-dependent survival function is unknown. We report here that the anti-apoptotic factor Bcl-2 is a downstream target that mediates ATF5-promoted cancer-cell survival in C6 glioma cells and MCF-7 breast cancer cells. ATF5 binds to an ATF5-specific regulatory element (ARE) that is downstream of and adjacent to the negative regulatory element (NRE) in the Bcl-2 P2 promoter, stimulating Bcl-2 expression. Highlighting the importance of Bcl-2 in ATF5-dependent cancer-cell survival, expression of Bcl-2 blocks death of C6 and MCF-7 cells induced by d/nATF5 and depletion of Bcl-2 impairs ATF5-promoted cell survival. Moreover, we found that Bcl-2 expression is not regulated by ATF5 in non-transformed rat astrocytes, MEFs, and human breast epithelial cells (HBEC), where knock-down of Bcl-2 but not that of ATF5 evokes cell death. These findings identify Bcl-2 as an essential mediator for ATF5's cancer-specific cell survival function in glioblastoma and breast cancer cells and provide direct evidence that the cell type-specific function of ATF5 derives from the differential regulation of downstream targets by ATF5 in different types of cells.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 17. doi:10.1158/1538-7445.AM2011-17" @default.
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- W2067148897 date "2011-04-15" @default.
- W2067148897 modified "2023-09-27" @default.
- W2067148897 title "Abstract 17: Bcl-2 is a downstream target of ATF5 that mediates ATF5's pro-survival function in a cell type-dependent manner" @default.
- W2067148897 doi "https://doi.org/10.1158/1538-7445.am2011-17" @default.
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