Abstract
Genes that are highly expressed in cancer cells and are essential for their viability are attractive targets for the development of novel cancer therapeutics. Activating transcription factor 5 (ATF5) is an anti-apoptotic protein that is highly expressed in malignant glioma but not normal brain tissues, and is essential for glioma cell survival. Recent work has revealed an essential survival pathway mediated by ATF5 in malignant glioma; pharmacological inhibition of this pathway leads to tumor regression in mice. ATF5 is also highly expressed in a variety of other cancers, and preliminary studies have shown that the ATF5-mediated survival pathway is active in diverse human cancer cell lines. Targeting this pathway may therefore have therapeutic implications for the treatment of a wide range of cancers. In this perspective, we summarize recent advances in ATF5 research, focusing on its role in promoting cancer and its potential as a target for cancer therapy.
Highlights
The mammalian activating transcription factor/ cyclic AMP responsive element-binding (ATF/CREB) family of transcription factors comprises a large group of proteins whose members have diverse roles in development, differentiation, cellular proliferation and apoptosis
Activating transcription factor 5 (ATF5), previously designated as ATFx, was first isolated as a binding partner of granulocyte colony-stimulating factor (G-CSF) gene promoter element 1-binding protein (GPE1-BP), a protein involved in regulating G-CSF expression [2]
Subsequent studies have revealed that ATF5 can either homodimerize or form heterodimers with ATF4 or CCAAT enhancerbinding protein (C/EBP), and bind CRE elements [3,4] or a recently-identified novel DNA motif with the consensus sequence C(C/T)TCT(T/C)CCTTA [5]
Summary
The mammalian activating transcription factor/ cyclic AMP responsive element-binding (ATF/CREB) family of transcription factors comprises a large group of proteins whose members have diverse roles in development, differentiation, cellular proliferation and apoptosis. A role for ATF5 in promoting cell survival was first suggested from gene expression profiling analysis in murine pro-B lymphocytic cells induced to undergo apoptosis following withdrawal of the cytokine interleukin-3 (IL-3) [7].
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