GADD45A

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Growth arrest and DNA-damage-inducible, alpha
NMR models gadd45alpha.jpg
PDB
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols GADD45A ; DDIT1; GADD45
External IDs OMIM126335 MGI107799 HomoloGene1449 GeneCards: GADD45A Gene
RNA expression pattern
PBB GE GADD45A 203725 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1647 13197
Ensembl ENSG00000116717 ENSMUSG00000036390
UniProt P24522 P48316
RefSeq (mRNA) NM_001199741 NM_007836
RefSeq (protein) NP_001186670 NP_031862
Location (UCSC) Chr 1:
68.15 – 68.15 Mb
Chr 6:
67.04 – 67.04 Mb
PubMed search [1] [2]

Growth arrest and DNA-damage-inducible protein GADD45 alpha is a protein that in humans is encoded by the GADD45A gene.[1][2][3]

Function[edit]

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.[3]

Applications[edit]

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.[4] 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[edit]

GADD45A has been shown to interact with:

See also[edit]

References[edit]

  1. ^ 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. 
  2. ^ 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. 
  3. ^ a b "Entrez Gene: GADD45A growth arrest and DNA-damage-inducible, alpha". 
  4. ^ 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. 
  5. ^ a b 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. 
  6. ^ a b 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. 
  7. ^ 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. 
  8. ^ a b c 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. 
  9. ^ a b 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. 
  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 (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. 
  11. ^ 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. 
  12. ^ 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. 
  13. ^ 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. 
  14. ^ 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. 
  15. ^ 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. 
  16. ^ 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[edit]