GADD45B explained

Growth arrest and DNA-damage-inducible, beta, also known as GADD45B, is a protein which in humans is encoded by the GADD45B gene.^{[1] [2] [3]}

Function

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]

Gadd45b is required for activity-induced DNA demethylation of specific promoters and expression of corresponding genes necessary for adult neurogenesis, including brain-derived neurotrophic factor and fibroblast growth factor. Hence GADD45B is implicated in affecting synaptic plasticity.^[4]

Interactions

GADD45B has been shown to interact with:

• ASK1,^[5]
• GADD45GIP1,^[6]
• MAP2K7^[5] and
• MAP3K4.

See also

• Gadd45

Further reading

• Abdollahi A, Lord KA, Hoffman-Liebermann B, Liebermann DA . Sequence and expression of a cDNA encoding MyD118: a novel myeloid differentiation primary response gene induced by multiple cytokines . Oncogene . 6 . 1 . 165–7 . Jan 1991 . 1899477 .
• Vairapandi M, Balliet AG, Fornace AJ, Hoffman B, Liebermann DA . 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 . Jun 1996 . 8700517 .
• Koonin EV . 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 . Apr 1997 . 9151207 .
• Takekawa M, Saito H . A family of stress-inducible GADD45-like proteins mediate activation of the stress-responsive MTK1/MEKK4 MAPKKK . Cell . 95 . 4 . 521–30 . Nov 1998 . 9827804 . 10.1016/S0092-8674(00)81619-0 . 18980341 . free .
• Sakaue M, Adachi H, Jetten AM . 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 . Apr 1999 . 10101024 .
• Gong R, Yu L, Zhang H, Tu Q, Zhao Y, Yang J, Xu Y, Zhao S . Assignment of human GADD45G to chromosome 9q22.1-->q22.3 by radiation hybrid mapping . Cytogenetics and Cell Genetics . 88 . 1–2 . 95–6 . 2000 . 10773677 . 10.1159/000015496 . 45495955 .
• Vairapandi M, Azam N, Balliet AG, Hoffman B, Liebermann DA . 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 . Jun 2000 . 10828065 . 10.1074/jbc.275.22.16810 . free .
• Yi YW, Kim D, Jung N, Hong SS, Lee HS, Bae I . Gadd45 family proteins are coactivators of nuclear hormone receptors . Biochemical and Biophysical Research Communications . 272 . 1 . 193–8 . May 2000 . 10872826 . 10.1006/bbrc.2000.2760 .
• Yang Q, Manicone A, Coursen JD, Linke SP, Nagashima M, Forgues M, Wang XW . Identification of a functional domain in a GADD45-mediated G2/M checkpoint . The Journal of Biological Chemistry . 275 . 47 . 36892–8 . Nov 2000 . 10973963 . 10.1074/jbc.M005319200 . free .
• Wan Y, Wang Z, Shao Y, Xu Y, Voorhees J, Fisher G . 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 . Dec 2000 . 11078829 . 10.3892/ijmm.6.6.683 .
• Kovalsky O, Lung FD, Roller PP, Fornace AJ . Oligomerization of human Gadd45a protein . The Journal of Biological Chemistry . 276 . 42 . 39330–9 . Oct 2001 . 11498536 . 10.1074/jbc.M105115200 . free .
• Vairapandi M, Balliet AG, Hoffman B, Liebermann DA . 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 . Sep 2002 . 12124778 . 10.1002/jcp.10140 . 19138273 .
• Jin R, De Smaele E, Zazzeroni F, Nguyen DU, Papa S, Jones J, Cox C, Gelinas C, Franzoso G . Regulation of the gadd45beta promoter by NF-kappaB . DNA and Cell Biology . 21 . 7 . 491–503 . Jul 2002 . 12162804 . 10.1089/104454902320219059 .
• 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 . CR6-interacting factor 1 interacts with Gadd45 family proteins and modulates the cell cycle . The Journal of Biological Chemistry . 278 . 30 . 28079–88 . Jul 2003 . 12716909 . 10.1074/jbc.M212835200 . free .
• Qiu W, David D, Zhou B, Chu PG, Zhang B, Wu M, Xiao J, Han T, Zhu Z, Wang T, Liu X, Lopez R, Frankel P, Jong A, Yen Y . Down-regulation of growth arrest DNA damage-inducible gene 45beta expression is associated with human hepatocellular carcinoma . The American Journal of Pathology . 162 . 6 . 1961–74 . Jun 2003 . 12759252 . 1868146 . 10.1016/s0002-9440(10)64329-5 .
• Zazzeroni F, Papa S, Algeciras-Schimnich A, Alvarez K, Melis T, Bubici C, Majewski N, Hay N, De Smaele E, Peter ME, Franzoso G . Gadd45 beta mediates the protective effects of CD40 costimulation against Fas-induced apoptosis . Blood . 102 . 9 . 3270–9 . Nov 2003 . 12855571 . 10.1182/blood-2003-03-0689 . free .
• Major MB, Jones DA . 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 . Feb 2004 . 14630914 . 10.1074/jbc.M311517200 . free .
• 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 . Gadd45 beta mediates the NF-kappa B suppression of JNK signalling by targeting MKK7/JNKK2 . Nature Cell Biology . 6 . 2 . 146–53 . Feb 2004 . 14743220 . 10.1038/ncb1093 . 5250125 .

Notes and References

1. Web site: Entrez Gene: GADD45B growth arrest and DNA-damage-inducible, beta.
2. Abdollahi A, Lord KA, Hoffman-Liebermann B, Liebermann DA . Sequence and expression of a cDNA encoding MyD118: a novel myeloid differentiation primary response gene induced by multiple cytokines . Oncogene . 6 . 1 . 165–7 . Jan 1991 . 1899477 .
3. Takekawa M, Saito H . A family of stress-inducible GADD45-like proteins mediate activation of the stress-responsive MTK1/MEKK4 MAPKKK . Cell . 95 . 4 . 521–30 . Nov 1998 . 9827804 . 10.1016/S0092-8674(00)81619-0 . 18980341 . free .
4. Ma DK, Jang MH, Guo JU, Kitabatake Y, Chang ML, Pow-Anpongkul N, Flavell RA, Lu B, Ming GL, Song H . Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis . Science . 323 . 5917 . 1074–7 . Feb 2009 . 19119186 . 2726986 . 10.1126/science.1166859 . 2009Sci...323.1074M .
5. 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 . Gadd45 beta mediates the NF-kappa B suppression of JNK signalling by targeting MKK7/JNKK2 . Nature Cell Biology . 6 . 2 . 146–53 . Feb 2004 . 14743220 . 10.1038/ncb1093 . 5250125 .
6. 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 . CR6-interacting factor 1 interacts with Gadd45 family proteins and modulates the cell cycle . The Journal of Biological Chemistry . 278 . 30 . 28079–88 . Jul 2003 . 12716909 . 10.1074/jbc.M212835200 . free .