This gene is a member of a group of genes whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. The genes in this group respond to environmental stresses by mediating activation of the p38/JNK pathway. This activation is mediated via their proteins binding and activating MTK1/MEKK4 kinase, which is an upstream activator of both p38 and JNK MAPKs. The function of these genes or their protein products is involved in the regulation of growth and apoptosis. These genes are regulated by different mechanisms, but they are often coordinately expressed and can function cooperatively in inhibiting cell growth.[1]
↑Abdollahi A, Lord KA, Hoffman-Liebermann B, Liebermann DA (Jan 1991). "Sequence and expression of a cDNA encoding MyD118: a novel myeloid differentiation primary response gene induced by multiple cytokines". Oncogene. 6 (1): 165–7. PMID1899477.
↑ 3.03.1Takekawa M, Saito H (Nov 1998). "A family of stress-inducible GADD45-like proteins mediate activation of the stress-responsive MTK1/MEKK4 MAPKKK". Cell. 95 (4): 521–30. doi:10.1016/S0092-8674(00)81619-0. PMID9827804.
↑ 5.05.1Papa S, Zazzeroni F, Bubici C, Jayawardena S, Alvarez K, Matsuda S, Nguyen DU, Pham CG, Nelsbach AH, Melis T, De Smaele E, Tang WJ, D'Adamio L, Franzoso G (Feb 2004). "Gadd45 beta mediates the NF-kappa B suppression of JNK signalling by targeting MKK7/JNKK2". Nature Cell Biology. 6 (2): 146–53. doi:10.1038/ncb1093. PMID14743220.
↑Chung HK, Yi YW, Jung NC, Kim D, Suh JM, Kim H, Park KC, Song JH, Kim DW, Hwang ES, Yoon SH, Bae YS, Kim JM, Bae I, Shong M (Jul 2003). "CR6-interacting factor 1 interacts with Gadd45 family proteins and modulates the cell cycle". The Journal of Biological Chemistry. 278 (30): 28079–88. doi:10.1074/jbc.M212835200. PMID12716909.
Further reading
Abdollahi A, Lord KA, Hoffman-Liebermann B, Liebermann DA (Jan 1991). "Sequence and expression of a cDNA encoding MyD118: a novel myeloid differentiation primary response gene induced by multiple cytokines". Oncogene. 6 (1): 165–7. PMID1899477.
Vairapandi M, Balliet AG, Fornace AJ, Hoffman B, Liebermann DA (Jun 1996). "The differentiation primary response gene MyD118, related to GADD45, encodes for a nuclear protein which interacts with PCNA and p21WAF1/CIP1". Oncogene. 12 (12): 2579–94. PMID8700517.
Koonin EV (Apr 1997). "Cell cycle and apoptosis: possible roles of Gadd45 and MyD118 proteins inferred from their homology to ribosomal proteins". Journal of Molecular Medicine. 75 (4): 236–8. PMID9151207.
Takekawa M, Saito H (Nov 1998). "A family of stress-inducible GADD45-like proteins mediate activation of the stress-responsive MTK1/MEKK4 MAPKKK". Cell. 95 (4): 521–30. doi:10.1016/S0092-8674(00)81619-0. PMID9827804.
Sakaue M, Adachi H, Jetten AM (Apr 1999). "Post-transcriptional regulation of MyD118 and GADD45 in human lung carcinoma cells during 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2- naphthalene carboxylic acid-induced apoptosis". Molecular Pharmacology. 55 (4): 668–76. PMID10101024.
Gong R, Yu L, Zhang H, Tu Q, Zhao Y, Yang J, Xu Y, Zhao S (2000). "Assignment of human GADD45G to chromosome 9q22.1-->q22.3 by radiation hybrid mapping". Cytogenetics and Cell Genetics. 88 (1–2): 95–6. doi:10.1159/000015496. PMID10773677.
Vairapandi M, Azam N, Balliet AG, Hoffman B, Liebermann DA (Jun 2000). "Characterization of MyD118, Gadd45, and proliferating cell nuclear antigen (PCNA) interacting domains. PCNA impedes MyD118 AND Gadd45-mediated negative growth control". The Journal of Biological Chemistry. 275 (22): 16810–9. doi:10.1074/jbc.275.22.16810. PMID10828065.
Yi YW, Kim D, Jung N, Hong SS, Lee HS, Bae I (May 2000). "Gadd45 family proteins are coactivators of nuclear hormone receptors". Biochemical and Biophysical Research Communications. 272 (1): 193–8. doi:10.1006/bbrc.2000.2760. PMID10872826.
Yang Q, Manicone A, Coursen JD, Linke SP, Nagashima M, Forgues M, Wang XW (Nov 2000). "Identification of a functional domain in a GADD45-mediated G2/M checkpoint". The Journal of Biological Chemistry. 275 (47): 36892–8. doi:10.1074/jbc.M005319200. PMID10973963.
Wan Y, Wang Z, Shao Y, Xu Y, Voorhees J, Fisher G (Dec 2000). "UV-induced expression of GADD45 is mediated by an oxidant sensitive pathway in cultured human keratinocytes and in human skin in vivo". International Journal of Molecular Medicine. 6 (6): 683–8. doi:10.3892/ijmm.6.6.683. PMID11078829.
Kovalsky O, Lung FD, Roller PP, Fornace AJ (Oct 2001). "Oligomerization of human Gadd45a protein". The Journal of Biological Chemistry. 276 (42): 39330–9. doi:10.1074/jbc.M105115200. PMID11498536.
Vairapandi M, Balliet AG, Hoffman B, Liebermann DA (Sep 2002). "GADD45b and GADD45g are cdc2/cyclinB1 kinase inhibitors with a role in S and G2/M cell cycle checkpoints induced by genotoxic stress". Journal of Cellular Physiology. 192 (3): 327–38. doi:10.1002/jcp.10140. PMID12124778.
Jin R, De Smaele E, Zazzeroni F, Nguyen DU, Papa S, Jones J, Cox C, Gelinas C, Franzoso G (Jul 2002). "Regulation of the gadd45beta promoter by NF-kappaB". DNA and Cell Biology. 21 (7): 491–503. doi:10.1089/104454902320219059. PMID12162804.
Chung HK, Yi YW, Jung NC, Kim D, Suh JM, Kim H, Park KC, Song JH, Kim DW, Hwang ES, Yoon SH, Bae YS, Kim JM, Bae I, Shong M (Jul 2003). "CR6-interacting factor 1 interacts with Gadd45 family proteins and modulates the cell cycle". The Journal of Biological Chemistry. 278 (30): 28079–88. doi:10.1074/jbc.M212835200. PMID12716909.
Zazzeroni F, Papa S, Algeciras-Schimnich A, Alvarez K, Melis T, Bubici C, Majewski N, Hay N, De Smaele E, Peter ME, Franzoso G (Nov 2003). "Gadd45 beta mediates the protective effects of CD40 costimulation against Fas-induced apoptosis". Blood. 102 (9): 3270–9. doi:10.1182/blood-2003-03-0689. PMID12855571.
Major MB, Jones DA (Feb 2004). "Identification of a gadd45beta 3' enhancer that mediates SMAD3- and SMAD4-dependent transcriptional induction by transforming growth factor beta". The Journal of Biological Chemistry. 279 (7): 5278–87. doi:10.1074/jbc.M311517200. PMID14630914.
Papa S, Zazzeroni F, Bubici C, Jayawardena S, Alvarez K, Matsuda S, Nguyen DU, Pham CG, Nelsbach AH, Melis T, De Smaele E, Tang WJ, D'Adamio L, Franzoso G (Feb 2004). "Gadd45 beta mediates the NF-kappa B suppression of JNK signalling by targeting MKK7/JNKK2". Nature Cell Biology. 6 (2): 146–53. doi:10.1038/ncb1093. PMID14743220.