GADD45A

GADD45A
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesGADD45A, DDIT1, GADD45, growth arrest and DNA damage inducible alpha
External IDsMGI: 107799 HomoloGene: 1449 GeneCards: GADD45A
Gene location (Human)
Chr.Chromosome 1 (human)[1]
Band1p31.3Start67,685,061 bp[1]
End67,688,338 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

1647

13197

Ensembl

ENSG00000116717

ENSMUSG00000036390

UniProt

P24522

P48316

RefSeq (mRNA)

NM_001924
NM_001199741
NM_001199742

NM_007836

RefSeq (protein)

NP_001186670
NP_001186671
NP_001915

NP_031862

Location (UCSC)Chr 1: 67.69 – 67.69 MbChr 6: 67.04 – 67.04 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Growth arrest and DNA-damage-inducible protein GADD45 alpha is a protein that in humans is encoded by the GADD45A gene.[5][6][7]

Function

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]

Applications

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.

Interactions

GADD45A has been shown to interact with:

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000116717 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000036390 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:".
  4. ↑ "Mouse PubMed Reference:".
  5. ↑ Papathanasiou MA, Kerr NC, Robbins JH, McBride OW, Alamo I Jr, Barrett SF, Hickson ID, Fornace AJ Jr (March 1991). "Induction by ionizing radiation of the gadd45 gene in cultured human cells: lack of mediation by protein kinase C". Mol Cell Biol. 11 (2): 1009–16. PMC 359769. PMID 1990262.
  6. ↑ Hollander MC, Alamo I, Jackman J, Wang MG, McBride OW, Fornace AJ Jr (December 1993). "Analysis of the mammalian gadd45 gene and its response to DNA damage". J Biol Chem. 268 (32): 24385–93. PMID 8226988.
  7. 1 2 "Entrez Gene: GADD45A growth arrest and DNA-damage-inducible, alpha".
  8. ↑ Walmsley RM, Tate M (2012). "The GADD45a-GFP GreenScreen HC assay". Methods Mol. Biol. 817: 231–50. doi:10.1007/978-1-61779-421-6_12. PMID 22147576.
  9. 1 2 Sánchez R, Pantoja-Uceda D, Prieto J, Diercks T, Marcaida MJ, Montoya G, Campos-Olivas R, Blanco FJ (July 2010). "Solution structure of human growth arrest and DNA damage 45alpha (Gadd45alpha) and its interactions with proliferating cell nuclear antigen (PCNA) and Aurora A kinase". J. Biol. Chem. 285 (29): 22196–201. doi:10.1074/jbc.M109.069344. PMC 2903397. PMID 20460379.
  10. 1 2 Zhan 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. PMID 10362260.
  11. ↑ Jin S, Antinore MJ, Lung FD, Dong X, Zhao H, Fan F, Colchagie AB, Blanck P, Roller PP, Fornace AJ, Zhan Q (June 2000). "The GADD45 inhibition of Cdc2 kinase correlates with GADD45-mediated growth suppression". J. Biol. Chem. 275 (22): 16602–8. doi:10.1074/jbc.M000284200. PMID 10747892.
  12. 1 2 3 Yang Q, Manicone A, Coursen JD, Linke SP, Nagashima M, Forgues M, Wang XW (November 2000). "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.
  13. 1 2 Vairapandi 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. PMID 12124778.
  14. ↑ 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 (July 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.
  15. ↑ 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.
  16. ↑ 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. PMID 10912791.
  17. ↑ Smith ML, Chen IT, Zhan Q, Bae I, Chen CY, Gilmer TM, Kastan MB, O'Connor PM, Fornace AJ (November 1994). "Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen". Science. 266 (5189): 1376–80. doi:10.1126/science.7973727. PMID 7973727.
  18. ↑ 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. PMID 7478510.
  19. ↑ Vairapandi M, Azam N, Balliet AG, Hoffman B, Liebermann DA (June 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.
  20. ↑ 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. PMID 7784094.

Further reading

  • Hildesheim J, Fornace AJ (2003). "Gadd45a: an elusive yet attractive candidate gene in pancreatic cancer". Clin. Cancer Res. 8 (8): 2475–9. PMID 12171872.
  • 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. PMID 7478510.
  • 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. PMID 7478594.
  • Hall PA, Kearsey JM, Coates PJ, et al. (1995). "Characterisation of the interaction between PCNA and Gadd45". Oncogene. 10 (12): 2427–33. PMID 7784094.
  • Carrier F, Smith ML, Bae I, et al. (1995). "Characterization of human Gadd45, a p53-regulated protein". J. Biol. Chem. 269 (51): 32672–7. PMID 7798274.
  • Smith ML, Chen IT, Zhan Q, et al. (1994). "Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen". Science. 266 (5189): 1376–80. doi:10.1126/science.7973727. PMID 7973727.
  • 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. PMID 9178907.
  • Warbrick E, Heatherington W, Lane DP, Glover DM (1998). "PCNA binding proteins in Drosophila melanogaster : the analysis of a conserved PCNA binding domain". Nucleic Acids Res. 26 (17): 3925–32. doi:10.1093/nar/26.17.3925. PMC 147798. PMID 9705499.
  • 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.
  • Carrier F, Georgel PT, Pourquier P, et al. (1999). "Gadd45, a p53-responsive stress protein, modifies DNA accessibility on damaged chromatin". Mol. Cell. Biol. 19 (3): 1673–85. PMC 83961. PMID 10022855.
  • 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. PMID 10362260.
  • Jin S, Antinore MJ, Lung FD, et al. (2000). "The GADD45 inhibition of Cdc2 kinase correlates with GADD45-mediated growth suppression". J. Biol. Chem. 275 (22): 16602–8. doi:10.1074/jbc.M000284200. PMID 10747892.
  • 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.
  • 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. PMID 10912791.
  • 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.
  • Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
  • 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.
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