This gene is a member of a group of genes, the GADD45 genes, whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents (mutagens). The DNA damage-induced transcription of this gene is mediated by both p53-dependent and -independent mechanisms. The protein encoded by this gene responds to environmental stresses by mediating activation of the p38/JNK pathway via MTK1/MEKK4 kinase.[7]
The fact that expression of this gene is an indicator of DNA damage has been exploited to construct an in vitro test for mutagenicity, the GADD45a-GFP GreenScreen HC assay.[8] This assay consists of a cell line which has been engineered so that expression of GADD45A will lead to expression of green fluorescent protein, which can easily be detected. To test a substance for mutagenicity, it is applied to these cells and fluorescence is measured.
^Walmsley RM, Tate M (2012). "The GADD45a-GFP GreenScreen HC assay". Genetic Toxicology. Methods in Molecular Biology. Vol. 817. pp. 231–50. doi:10.1007/978-1-61779-421-6_12. ISBN 978-1-61779-420-9. PMID22147576.
^ abZhan Q, Antinore MJ, Wang XW, Carrier F, Smith ML, Harris CC, Fornace AJ (May 1999). "Association with Cdc2 and inhibition of Cdc2/Cyclin B1 kinase activity by the p53-regulated protein Gadd45". Oncogene. 18 (18): 2892–900. doi:10.1038/sj.onc.1202667. PMID10362260. S2CID13112302.
^ abVairapandi M, Balliet AG, Hoffman B, Liebermann DA (September 2002). "GADD45b and GADD45g are cdc2/cyclinB1 kinase inhibitors with a role in S and G2/M cell cycle checkpoints induced by genotoxic stress". J. Cell. Physiol. 192 (3): 327–38. doi:10.1002/jcp.10140. PMID12124778. S2CID19138273.
^Zhao H, Jin S, Antinore MJ, Lung FD, Fan F, Blanck P, Roller P, Fornace AJ, Zhan Q (July 2000). "The central region of Gadd45 is required for its interaction with p21/WAF1". Exp. Cell Res. 258 (1): 92–100. doi:10.1006/excr.2000.4906. PMID10912791.
^Chen IT, Smith ML, O'Connor PM, Fornace AJ (November 1995). "Direct interaction of Gadd45 with PCNA and evidence for competitive interaction of Gadd45 and p21Waf1/Cip1 with PCNA". Oncogene. 11 (10): 1931–7. PMID7478510.
^Hall PA, Kearsey JM, Coates PJ, Norman DG, Warbrick E, Cox LS (June 1995). "Characterisation of the interaction between PCNA and Gadd45". Oncogene. 10 (12): 2427–33. PMID7784094.
Hildesheim J, Fornace AJ (2003). "Gadd45a: an elusive yet attractive candidate gene in pancreatic cancer". Clin. Cancer Res. 8 (8): 2475–9. PMID12171872.
Chen IT, Smith ML, O'Connor PM, Fornace AJ (1995). "Direct interaction of Gadd45 with PCNA and evidence for competitive interaction of Gadd45 and p21Waf1/Cip1 with PCNA". Oncogene. 11 (10): 1931–7. PMID7478510.
Kearsey JM, Coates PJ, Prescott AR, et al. (1995). "Gadd45 is a nuclear cell cycle regulated protein which interacts with p21Cip1". Oncogene. 11 (9): 1675–83. PMID7478594.
Hall PA, Kearsey JM, Coates PJ, et al. (1995). "Characterisation of the interaction between PCNA and Gadd45". Oncogene. 10 (12): 2427–33. PMID7784094.
Warbrick E, Lane DP, Glover DM, Cox LS (1997). "Homologous regions of Fen1 and p21Cip1 compete for binding to the same site on PCNA: a potential mechanism to co-ordinate DNA replication and repair". Oncogene. 14 (19): 2313–21. doi:10.1038/sj.onc.1201072. PMID9178907. S2CID29525059.
Zhan Q, Antinore MJ, Wang XW, et al. (1999). "Association with Cdc2 and inhibition of Cdc2/Cyclin B1 kinase activity by the p53-regulated protein Gadd45". Oncogene. 18 (18): 2892–900. doi:10.1038/sj.onc.1202667. PMID10362260. S2CID13112302.
Yi YW, Kim D, Jung N, et al. (2000). "Gadd45 family proteins are coactivators of nuclear hormone receptors". Biochem. Biophys. Res. Commun. 272 (1): 193–8. doi:10.1006/bbrc.2000.2760. PMID10872826.
Zhao H, Jin S, Antinore MJ, et al. (2000). "The central region of Gadd45 is required for its interaction with p21/WAF1". Exp. Cell Res. 258 (1): 92–100. doi:10.1006/excr.2000.4906. PMID10912791.