Differential usage of alternate promoters of the human stress response gene ATF3 in stress response and cancer cells
Open Access
- 9 January 2009
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 37 (5), 1438-1451
- https://doi.org/10.1093/nar/gkn1082
Abstract
Stress response gene ATF3 plays a pleiotropic role in determining cell fate in response to mitogenic or stress stimuli. An alternate promoter of the human ATF3 gene (designated P1 in this study) has recently been reported, which is located ∼43.5 kb upstream of the previously reported P2 promoter. We showed here that the P1 promoter is highly conserved between human and mouse and is functional in response to various stimuli, whereas the P1 promoter was dominantly induced by serum and the P2 promoter was more efficiently activated in response to TGF-β and oncogenic HRAS . The P1 promoter contains multiple transcriptional start sites, and the different 5′-UTRs markedly affected their translation in response to stress. In human prostate and Hodgkin Reed–Sternberg cancer cells with elevated expression of ATF3, the P1 promoter was constitutively activated and its chromatin structure was modified into active configuration. The differential usage of alternate promoters of the ATF3 gene at both transcriptional and translational level and the modification of chromatin structure may provide a novel mechanism for expressing ATF3 in determining cell fate during stress response and cancer.This publication has 45 references indexed in Scilit:
- Activating transcription factor 3 is a negative regulator of allergic pulmonary inflammationThe Journal of Experimental Medicine, 2008
- ATF3 regulates MCMV infection in mice by modulating IFN-γ expression in natural killer cellsProceedings of the National Academy of Sciences of the United States of America, 2008
- The regulation of ATF3 gene expression by mitogen-activated protein kinasesBiochemical Journal, 2006
- The Tumor Metastasis Suppressor Gene Drg-1 Down-regulates the Expression of Activating Transcription Factor 3 in Prostate CancerCancer Research, 2006
- Activation of the ATF3 gene through a co-ordinated amino acid-sensing response programme that controls transcriptional regulation of responsive genes following amino acid limitationBiochemical Journal, 2006
- Activating Transcription Factor 3, a Stress-inducible Gene, Suppresses Ras-stimulated TumorigenesisOnline Journal of Public Health Informatics, 2006
- Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genesGenome Research, 2005
- ATF3 induction following DNA damage is regulated by distinct signaling pathways and over-expression of ATF3 protein suppresses cells growthOncogene, 2002
- Transcription factor ATF3 partially transforms chick embryo fibroblasts by promoting growth factor-independent proliferationOncogene, 2001
- The Transcriptional Program in the Response of Human Fibroblasts to SerumScience, 1999