GADD45B

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Growth arrest and DNA-damage-inducible, beta
Identifiers
Symbols GADD45B ; GADD45BETA; MYD118
External IDs OMIM604948 MGI107776 HomoloGene7433 GeneCards: GADD45B Gene
RNA expression pattern
PBB GE GADD45B 207574 s at tn.png
PBB GE GADD45B 209304 x at tn.png
PBB GE GADD45B 209305 s at tn.png
More reference expression data
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 [1] [2]

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[edit]

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[edit]

GADD45B has been shown to interact with MAP3K4,[3] ASK1,[5] MAP2K7[5] and GADD45GIP1.[6]

See also[edit]

References[edit]

  1. ^ a b "Entrez Gene: GADD45B growth arrest and DNA-damage-inducible, beta". 
  2. ^ Abdollahi A, Lord KA, Hoffman-Liebermann B, Liebermann DA (January 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. 
  3. ^ a b Takekawa M, Saito H (November 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. 
  4. ^ Ma DK, Jang MH, Guo JU, Kitabatake Y, Chang ML, Pow-Anpongkul N, Flavell RA, Lu B, Ming GL, Song H (February 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. 
  5. ^ a b Papa, Salvatore; Zazzeroni Francesca, Bubici Concetta, Jayawardena Shanthi, Alvarez Kellean, Matsuda Shuji, Nguyen Dung U, Pham Can G, Nelsbach Andreas H, Melis Tiziana, De Smaele Enrico, Tang Wei-Jen, D'Adamio Luciano, Franzoso Guido (Feb 2004). "Gadd45 beta mediates the NF-kappa B suppression of JNK signalling by targeting MKK7/JNKK2". Nat. Cell Biol. (England) 6 (2): 146–53. doi:10.1038/ncb1093. ISSN 1465-7392. PMID 14743220. 
  6. ^ Chung, Hyo Kyun; Yi Yong-Weon, Jung Neon-Cheol, Kim Daegun, Suh Jae Mi, Kim Ho, Park Ki Cheol, Song Jung Hun, Kim Dong Wook, Hwang Eun Suk, Yoon Soo-Hyun, Bae Young-Seuk, Kim Jin Man, Bae Insoo, Shong Minho (Jul 2003). "CR6-interacting factor 1 interacts with Gadd45 family proteins and modulates the cell cycle". J. Biol. Chem. (United States) 278 (30): 28079–88. doi:10.1074/jbc.M212835200. ISSN 0021-9258. PMID 12716909. 

Further reading[edit]

  • Abdollahi A, Lord KA, Hoffman-Liebermann B, Liebermann DA (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, et al. (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 (1997). "Cell cycle and apoptosis: possible roles of Gadd45 and MyD118 proteins inferred from their homology to ribosomal proteins.". J. Mol. Med. 75 (4): 236–8. PMID 9151207. 
  • Takekawa M, Saito H (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 (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.". Mol. Pharmacol. 55 (4): 668–76. PMID 10101024. 
  • Gong R, Yu L, Zhang H, et al. (2000). "Assignment of human GADD45G to chromosome 9q22.1→q22.3 by radiation hybrid mapping.". Cytogenet. Cell Genet. 88 (1–2): 95–6. doi:10.1159/000015496. PMID 10773677. 
  • Vairapandi M, Azam N, Balliet AG, et al. (2000). "Characterization of MyD118, Gadd45, and proliferating cell nuclear antigen (PCNA) interacting domains. PCNA impedes MyD118 AND Gadd45-mediated negative growth control". J. Biol. Chem. 275 (22): 16810–9. doi:10.1074/jbc.275.22.16810. PMID 10828065. 
  • 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. PMID 10872826. 
  • Yang Q, Manicone A, Coursen JD, et al. (2001). "Identification of a functional domain in a GADD45-mediated G2/M checkpoint". J. Biol. Chem. 275 (47): 36892–8. doi:10.1074/jbc.M005319200. PMID 10973963. 
  • Wan Y, Wang Z, Shao Y, et al. (2001). "UV-induced expression of GADD45 is mediated by an oxidant sensitive pathway in cultured human keratinocytes and in human skin in vivo". Int. J. Mol. Med. 6 (6): 683–8. doi:10.3892/ijmm.6.6.683. PMID 11078829. 
  • Kovalsky O, Lung FD, Roller PP, Fornace AJ (2001). "Oligomerization of human Gadd45a protein". J. Biol. Chem. 276 (42): 39330–9. doi:10.1074/jbc.M105115200. PMID 11498536. 
  • Vairapandi M, Balliet AG, Hoffman B, Liebermann DA (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. PMID 12124778. 
  • Jin R, De Smaele E, Zazzeroni F, et al. (2002). "Regulation of the gadd45beta promoter by NF-kappaB". DNA Cell Biol. 21 (7): 491–503. doi:10.1089/104454902320219059. PMID 12162804. 
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. 
  • Chung HK, Yi YW, Jung NC, et al. (2003). "CR6-interacting factor 1 interacts with Gadd45 family proteins and modulates the cell cycle". J. Biol. Chem. 278 (30): 28079–88. doi:10.1074/jbc.M212835200. PMID 12716909. 
  • Qiu W, David D, Zhou B, et al. (2003). "Down-regulation of growth arrest DNA damage-inducible gene 45beta expression is associated with human hepatocellular carcinoma". Am. J. Pathol. 162 (6): 1961–74. doi:10.1016/s0002-9440(10)64329-5. PMC 1868146. PMID 12759252. 
  • Zazzeroni F, Papa S, Algeciras-Schimnich A, et al. (2004). "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 (2004). "Identification of a gadd45beta 3' enhancer that mediates SMAD3- and SMAD4-dependent transcriptional induction by transforming growth factor beta". J. Biol. Chem. 279 (7): 5278–87. doi:10.1074/jbc.M311517200. PMID 14630914. 
  • Papa S, Zazzeroni F, Bubici C, et al. (2004). "Gadd45 beta mediates the NF-kappa B suppression of JNK signalling by targeting MKK7/JNKK2". Nat. Cell Biol. 6 (2): 146–53. doi:10.1038/ncb1093. PMID 14743220. 
  • Grimwood J, Gordon LA, Olsen A, et al. (2004). "The DNA sequence and biology of human chromosome 19". Nature 428 (6982): 529–35. doi:10.1038/nature02399. PMID 15057824.