GADD45A

{{Short description|Protein-coding gene in the species Homo sapiens}}

Growth arrest and DNA-damage-inducible protein GADD45 alpha is a protein that in humans is encoded by the GADD45A gene.{{cite journal |vauthors=Papathanasiou MA, Kerr NC, Robbins JH, McBride OW, ((Alamo I Jr)), Barrett SF, Hickson ID, ((Fornace AJ Jr)) | title = Induction by ionizing radiation of the gadd45 gene in cultured human cells: lack of mediation by protein kinase C | journal = Mol Cell Biol | volume = 11 | issue = 2 | pages = 1009–16 |date=March 1991 | pmid = 1990262 | pmc = 359769 | doi = 10.1128/MCB.11.2.1009}}{{cite journal |vauthors=Hollander MC, Alamo I, Jackman J, Wang MG, McBride OW, ((Fornace AJ Jr)) | title = Analysis of the mammalian gadd45 gene and its response to DNA damage | journal = J Biol Chem | volume = 268 | issue = 32 | pages = 24385–93 |date=December 1993 | doi = 10.1016/S0021-9258(20)80537-7 | pmid = 8226988 | doi-access = free }}{{cite web | title = Entrez Gene: GADD45A growth arrest and DNA-damage-inducible, alpha| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1647}}

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.

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.{{cite book |vauthors=Walmsley RM, Tate M | title = Genetic Toxicology | chapter = The GADD45a-GFP GreenScreen HC assay | volume = 817 | pages = 231–50 | year = 2012 | pmid = 22147576 | doi = 10.1007/978-1-61779-421-6_12 | series = Methods in Molecular Biology | isbn = 978-1-61779-420-9 }} 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:

AURKA,{{cite journal | date = July 2010 |vauthors=Sánchez R, Pantoja-Uceda D, Prieto J, Diercks T, Marcaida MJ, Montoya G, Campos-Olivas R, Blanco FJ | title = Solution structure of human growth arrest and DNA damage 45alpha (Gadd45alpha) and its interactions with proliferating cell nuclear antigen (PCNA) and Aurora A kinase | journal = J. Biol. Chem. | volume = 285 | issue = 29 | pages = 22196–201 | pmid = 20460379 | pmc = 2903397 | doi = 10.1074/jbc.M109.069344|doi-access=free }}
Cdk1,{{cite journal | date = May 1999 |vauthors=Zhan Q, Antinore MJ, Wang XW, Carrier F, Smith ML, Harris CC, Fornace AJ | title = Association with Cdc2 and inhibition of Cdc2/Cyclin B1 kinase activity by the p53-regulated protein Gadd45 | journal = Oncogene | volume = 18 | issue = 18 | pages = 2892–900 | pmid = 10362260 | doi = 10.1038/sj.onc.1202667|s2cid=13112302 | doi-access = }}{{cite journal | date = June 2000 |vauthors=Jin S, Antinore MJ, Lung FD, Dong X, Zhao H, Fan F, Colchagie AB, Blanck P, Roller PP, Fornace AJ, Zhan Q | title = The GADD45 inhibition of Cdc2 kinase correlates with GADD45-mediated growth suppression | journal = J. Biol. Chem. | volume = 275 | issue = 22 | pages = 16602–8 | pmid = 10747892 | doi = 10.1074/jbc.M000284200| doi-access = free }}{{cite journal | date = November 2000 |vauthors=Yang Q, Manicone A, Coursen JD, Linke SP, Nagashima M, Forgues M, Wang XW | title = Identification of a functional domain in a GADD45-mediated G2/M checkpoint | journal = J. Biol. Chem. | volume = 275 | issue = 47 | pages = 36892–8 | pmid = 10973963 | doi = 10.1074/jbc.M005319200| doi-access = free }}{{cite journal | date = September 2002 |vauthors=Vairapandi M, Balliet AG, Hoffman B, Liebermann DA | title = GADD45b and GADD45g are cdc2/cyclinB1 kinase inhibitors with a role in S and G2/M cell cycle checkpoints induced by genotoxic stress | journal = J. Cell. Physiol. | volume = 192 | issue = 3 | pages = 327–38 | pmid = 12124778 | doi = 10.1002/jcp.10140|s2cid=19138273 }}
CCNB1,
GADD45GIP1{{cite journal | date = July 2003 |vauthors=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 | title = CR6-interacting factor 1 interacts with Gadd45 family proteins and modulates the cell cycle | journal = J. Biol. Chem. | volume = 278 | issue = 30 | pages = 28079–88 | pmid = 12716909 | doi = 10.1074/jbc.M212835200| doi-access = free }}
MAP3K4,{{cite journal | date = November 1998 |vauthors=Takekawa M, Saito H | title = A family of stress-inducible GADD45-like proteins mediate activation of the stress-responsive MTK1/MEKK4 MAPKKK | journal = Cell | volume = 95 | issue = 4 | pages = 521–30 | pmid = 9827804 | doi = 10.1016/s0092-8674(00)81619-0|s2cid=18980341 | doi-access = free }}
P21,{{cite journal | date = July 2000 |vauthors=Zhao H, Jin S, Antinore MJ, Lung FD, Fan F, Blanck P, Roller P, Fornace AJ, Zhan Q | title = The central region of Gadd45 is required for its interaction with p21/WAF1 | journal = Exp. Cell Res. | volume = 258 | issue = 1 | pages = 92–100 | pmid = 10912791 | doi = 10.1006/excr.2000.4906}} and
PCNA.{{cite journal | date = November 1994 |vauthors=Smith ML, Chen IT, Zhan Q, Bae I, Chen CY, Gilmer TM, Kastan MB, O'Connor PM, Fornace AJ | title = Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen | journal = Science | volume = 266 | issue = 5189 | pages = 1376–80 | pmid = 7973727 | doi = 10.1126/science.7973727|bibcode=1994Sci...266.1376S |url=https://zenodo.org/record/1231241 }}{{cite journal | date = November 1995 |vauthors=Chen IT, Smith ML, O'Connor PM, Fornace AJ | title = Direct interaction of Gadd45 with PCNA and evidence for competitive interaction of Gadd45 and p21Waf1/Cip1 with PCNA | journal = Oncogene | volume = 11 | issue = 10 | pages = 1931–7 | pmid = 7478510 }}{{cite journal | date = June 2000 |vauthors=Vairapandi M, Azam N, Balliet AG, Hoffman B, Liebermann DA | title = Characterization of MyD118, Gadd45, and proliferating cell nuclear antigen (PCNA) interacting domains. PCNA impedes MyD118 AND Gadd45-mediated negative growth control | journal = J. Biol. Chem. | volume = 275 | issue = 22 | pages = 16810–9 | pmid = 10828065 | doi = 10.1074/jbc.275.22.16810| doi-access = free }}{{cite journal | date = June 1995 |vauthors=Hall PA, Kearsey JM, Coates PJ, Norman DG, Warbrick E, Cox LS | title = Characterisation of the interaction between PCNA and Gadd45 | journal = Oncogene | volume = 10 | issue = 12 | pages = 2427–33 | pmid = 7784094 }}

References

External links

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