GADD45B

Growth arrest and DNA-damage-inducible, beta, also known as GADD45B, is a protein which in humans is encoded by the GADD45B gene.[5][6][7]

GADD45B
Identifiers
Aliases	GADD45B, GADD45BETA, MYD118, growth arrest and DNA damage inducible beta
External IDs	OMIM: 604948 MGI: 107776 HomoloGene: 7433 GeneCards: GADD45B
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.3 Start 2,476,122 bp[1] End 2,478,259 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10 C1|10 39.72 cM Start 80,930,073 bp[2] End 80,932,204 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001948 protein binding Cellular component • cytoplasm • cell nucleus Biological process • multicellular organism development • positive regulation of apoptotic process • positive regulation of p38MAPK cascade • response to stress • cell differentiation • positive regulation of JNK cascade • activation of MAPKKK activity • negative regulation of protein kinase activity • activation of MAPKK activity • apoptotic process • regulation of cell cycle Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	4616	17873
Ensembl	ENSG00000099860	ENSMUSG00000015312
UniProt	O75293	P22339
RefSeq (mRNA)	NM_015675	NM_008655
RefSeq (protein)	NP_056490	NP_032681
Location (UCSC)	Chr 19: 2.48 – 2.48 Mb	Chr 10: 80.93 – 80.93 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[5]

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.[8]

Interactions

GADD45B has been shown to interact with:

• ASK1,[9]
• GADD45GIP1,[10]
• MAP2K7[9] and
• MAP3K4.[7]

See also

• Gadd45

References

1. GRCh38: Ensembl release 89: ENSG00000099860 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000015312 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: GADD45B growth arrest and DNA-damage-inducible, beta".
6. 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. PMID 1899477.
7. 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. PMID 9827804.
8. Ma DK, Jang MH, Guo JU, Kitabatake Y, Chang ML, Pow-Anpongkul N, Flavell RA, Lu B, Ming GL, Song H (Feb 2009). "Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis". Science. 323 (5917): 1074–7. doi:10.1126/science.1166859. PMC 2726986. PMID 19119186.
9. 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. PMID 14743220.
10. 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. PMID 12716909.

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. PMID 1899477.
• 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. PMID 8700517.
• 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. PMID 9151207.
• 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. PMID 9827804.
• 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. PMID 10101024.
• 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. PMID 10773677.
• 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. PMID 10828065.
• 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. PMID 10872826.
• 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. PMID 10973963.
• 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. PMID 11078829.
• 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. PMID 11498536.
• 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. PMID 12124778.
• 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. PMID 12162804.
• 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. PMID 12716909.
• 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 (Jun 2003). "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. doi:10.1016/s0002-9440(10)64329-5. PMC 1868146. PMID 12759252.
• 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. PMID 12855571.
• 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. PMID 14630914.
• 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. PMID 14743220.