GADD45A: Difference between revisions

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{{Infobox_gene}}
{{PBB_Controls
'''Growth arrest and DNA-damage-inducible protein GADD45 alpha''' is a [[protein]] that in humans is encoded by the ''GADD45A'' [[gene]].<ref name="pmid1990262">{{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 =  }}</ref><ref name="pmid8226988">{{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 | pmid = 8226988 }}</ref><ref name="entrez">{{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| accessdate = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
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 ([[mutagen]]s). 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 mitogen-activated protein kinases|p38]]/[[JNK]] pathway via [[MAP3K4|MTK1/MEKK4]] kinase.<ref name="entrez" />
| image =
| image_source =
| PDB =  
| Name = Growth arrest and DNA-damage-inducible, alpha
| HGNCid = 4095
| Symbol = GADD45A
| AltSymbols =; DDIT1; GADD45
| OMIM = 126335
| ECnumber = 
| Homologene = 1449
| MGIid = 107799
| GeneAtlas_image1 = PBB_GE_GADD45A_203725_at_tn.png
| Function = {{GNF_GO|id=GO:0005515 |text = protein binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}}
| Process = {{GNF_GO|id=GO:0000079 |text = regulation of cyclin-dependent protein kinase activity}} {{GNF_GO|id=GO:0006281 |text = DNA repair}} {{GNF_GO|id=GO:0006469 |text = negative regulation of protein kinase activity}} {{GNF_GO|id=GO:0006915 |text = apoptosis}} {{GNF_GO|id=GO:0007049 |text = cell cycle}} {{GNF_GO|id=GO:0007050 |text = cell cycle arrest}} {{GNF_GO|id=GO:0007098 |text = centrosome cycle}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 1647
    | Hs_Ensembl = ENSG00000116717
    | Hs_RefseqProtein = NP_001915
    | Hs_RefseqmRNA = NM_001924
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 1
    | Hs_GenLoc_start = 67923332
    | Hs_GenLoc_end = 67926609
    | Hs_Uniprot = P24522
    | Mm_EntrezGene = 13197
    | Mm_Ensembl = ENSMUSG00000036390
    | Mm_RefseqmRNA = NM_007836
    | Mm_RefseqProtein = NP_031862
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 6
    | Mm_GenLoc_start = 66964674
    | Mm_GenLoc_end = 66966985
    | Mm_Uniprot = Q3UMH6
  }}
}}
'''Growth arrest and DNA-damage-inducible, alpha''', also known as '''GADD45A''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: GADD45A growth arrest and DNA-damage-inducible, alpha| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1647| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Applications ==
{{PBB_Summary
 
| section_title =  
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.<ref name="pmid22147576">{{cite journal |vauthors=Walmsley RM, Tate M | title = The GADD45a-GFP GreenScreen HC assay | journal = Methods Mol. Biol. | volume = 817 | issue = | pages = 231–50 | year = 2012 | pmid = 22147576 | doi = 10.1007/978-1-61779-421-6_12 }}</ref> 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.
| summary_text = 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 protein encoded by this gene responds to environmental stresses by mediating activation of the p38/JNK pathway via MTK1/MEKK4 kinase. The DNA damage-induced transcription of this gene is mediated by both p53-dependent and -independent mechanisms.<ref name="entrez">{{cite web | title = Entrez Gene: GADD45A growth arrest and DNA-damage-inducible, alpha| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1647| accessdate = }}</ref>
 
}}
== Interactions ==
 
GADD45A has been shown to [[Protein-protein interaction|interact]] with:
* [[Aurora A kinase|AURKA]],<ref name = pmid20460379>{{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}}</ref><ref name = pmid20460379/>
* [[Cdk1]],<ref name = pmid10362260>{{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}}</ref><ref name = pmid10747892>{{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}}</ref><ref name = pmid10973963>{{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}}</ref><ref name = pmid12124778>{{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}}</ref>
* [[Cyclin B1|CCNB1]],<ref name = pmid10362260/><ref name = pmid12124778/>
* [[GADD45GIP1]]<ref name = pmid12716909>{{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}}</ref>
* [[MAP3K4]],<ref name = pmid9827804>{{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}}</ref>
* [[P21]],<ref name = pmid10973963/><ref name = pmid10912791>{{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}}</ref> and
* [[PCNA]].<ref name = pmid10973963/><ref name = pmid7973727>{{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}}</ref><ref name = pmid7478510>{{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 | doi = }}</ref><ref name = pmid10828065>{{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}}</ref><ref name = pmid7784094>{{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 | doi = }}</ref>


==See also==
==See also==
Line 58: Line 24:


==References==
==References==
{{reflist|2}}
{{reflist}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
*{{cite journal  |vauthors=Hildesheim J, Fornace AJ |title=Gadd45a: an elusive yet attractive candidate gene in pancreatic cancer. |journal=Clin. Cancer Res. |volume=8 |issue= 8 |pages= 2475–9 |year= 2003 |pmid= 12171872 |doi=  }}
| citations =
*{{cite journal  |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 |year= 1995 |pmid= 7478510 |doi=  }}
*{{cite journal  | author=Hildesheim J, Fornace AJ |title=Gadd45a: an elusive yet attractive candidate gene in pancreatic cancer. |journal=Clin. Cancer Res. |volume=8 |issue= 8 |pages= 2475-9 |year= 2003 |pmid= 12171872 |doi=  }}
*{{cite journal  |vauthors=Kearsey JM, Coates PJ, Prescott AR |title=Gadd45 is a nuclear cell cycle regulated protein which interacts with p21Cip1. |journal=Oncogene |volume=11 |issue= 9 |pages= 1675–83 |year= 1995 |pmid= 7478594 |doi=  |display-authors=etal}}
*{{cite journal  | author=Papathanasiou MA, Kerr NC, Robbins JH, ''et al.'' |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 |year= 1991 |pmid= 1990262 |doi=  }}
*{{cite journal  |vauthors=Hall PA, Kearsey JM, Coates PJ |title=Characterisation of the interaction between PCNA and Gadd45. |journal=Oncogene |volume=10 |issue= 12 |pages= 2427–33 |year= 1995 |pmid= 7784094 |doi=  |display-authors=etal}}
*{{cite journal  | author=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 |year= 1995 |pmid= 7478510 |doi=  }}
*{{cite journal  |vauthors=Carrier F, Smith ML, Bae I |title=Characterization of human Gadd45, a p53-regulated protein. |journal=J. Biol. Chem. |volume=269 |issue= 51 |pages= 32672–7 |year= 1995 |pmid= 7798274 |doi=  |display-authors=etal}}
*{{cite journal  | author=Kearsey JM, Coates PJ, Prescott AR, ''et al.'' |title=Gadd45 is a nuclear cell cycle regulated protein which interacts with p21Cip1. |journal=Oncogene |volume=11 |issue= 9 |pages= 1675-83 |year= 1995 |pmid= 7478594 |doi=  }}
*{{cite journal  |vauthors=Smith ML, Chen IT, Zhan Q |title=Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen. |journal=Science |volume=266 |issue= 5189 |pages= 1376–80 |year= 1994 |pmid= 7973727 |doi=10.1126/science.7973727  |display-authors=etal}}
*{{cite journal  | author=Hall PA, Kearsey JM, Coates PJ, ''et al.'' |title=Characterisation of the interaction between PCNA and Gadd45. |journal=Oncogene |volume=10 |issue= 12 |pages= 2427-33 |year= 1995 |pmid= 7784094 |doi=  }}
*{{cite journal  |vauthors=Warbrick E, Lane DP, Glover DM, Cox LS |title=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. |journal=Oncogene |volume=14 |issue= 19 |pages= 2313–21 |year= 1997 |pmid= 9178907 |doi= 10.1038/sj.onc.1201072 }}
*{{cite journal  | author=Carrier F, Smith ML, Bae I, ''et al.'' |title=Characterization of human Gadd45, a p53-regulated protein. |journal=J. Biol. Chem. |volume=269 |issue= 51 |pages= 32672-7 |year= 1995 |pmid= 7798274 |doi=  }}
*{{cite journal  |vauthors=Warbrick E, Heatherington W, Lane DP, Glover DM |title=PCNA binding proteins in Drosophila melanogaster : the analysis of a conserved PCNA binding domain. |journal=Nucleic Acids Res. |volume=26 |issue= 17 |pages= 3925–32 |year= 1998 |pmid= 9705499 |doi=10.1093/nar/26.17.3925  | pmc=147798 }}
*{{cite journal  | author=Smith ML, Chen IT, Zhan Q, ''et al.'' |title=Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen. |journal=Science |volume=266 |issue= 5189 |pages= 1376-80 |year= 1994 |pmid= 7973727 |doi= }}
*{{cite journal  |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 |year= 1998 |pmid= 9827804 |doi=10.1016/S0092-8674(00)81619-0 }}
*{{cite journal  | author=Hollander MC, Alamo I, Jackman J, ''et al.'' |title=Analysis of the mammalian gadd45 gene and its response to DNA damage. |journal=J. Biol. Chem. |volume=268 |issue= 32 |pages= 24385-93 |year= 1993 |pmid= 8226988 |doi=  }}
*{{cite journal  |vauthors=Carrier F, Georgel PT, Pourquier P |title=Gadd45, a p53-responsive stress protein, modifies DNA accessibility on damaged chromatin. |journal=Mol. Cell. Biol. |volume=19 |issue= 3 |pages= 1673–85 |year= 1999 |pmid= 10022855 |doi=  | pmc=83961  |display-authors=etal}}
*{{cite journal  | author=Warbrick E, Lane DP, Glover DM, Cox LS |title=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. |journal=Oncogene |volume=14 |issue= 19 |pages= 2313-21 |year= 1997 |pmid= 9178907 |doi= 10.1038/sj.onc.1201072 }}
*{{cite journal  |vauthors=Zhan Q, Antinore MJ, Wang XW |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 |year= 1999 |pmid= 10362260 |doi= 10.1038/sj.onc.1202667 |display-authors=etal}}
*{{cite journal  | author=Warbrick E, Heatherington W, Lane DP, Glover DM |title=PCNA binding proteins in Drosophila melanogaster : the analysis of a conserved PCNA binding domain. |journal=Nucleic Acids Res. |volume=26 |issue= 17 |pages= 3925-32 |year= 1998 |pmid= 9705499 |doi=  }}
*{{cite journal  |vauthors=Jin S, Antinore MJ, Lung FD |title=The GADD45 inhibition of Cdc2 kinase correlates with GADD45-mediated growth suppression. |journal=J. Biol. Chem. |volume=275 |issue= 22 |pages= 16602–8 |year= 2000 |pmid= 10747892 |doi= 10.1074/jbc.M000284200 |display-authors=etal}}
*{{cite journal  | author=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 |year= 1998 |pmid= 9827804 |doi=  }}
*{{cite journal  |vauthors=Vairapandi M, Azam N, Balliet AG |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 |year= 2000 |pmid= 10828065 |doi=10.1074/jbc.275.22.16810 |display-authors=etal}}
*{{cite journal  | author=Carrier F, Georgel PT, Pourquier P, ''et al.'' |title=Gadd45, a p53-responsive stress protein, modifies DNA accessibility on damaged chromatin. |journal=Mol. Cell. Biol. |volume=19 |issue= 3 |pages= 1673-85 |year= 1999 |pmid= 10022855 |doi=  }}
*{{cite journal  |vauthors=Yi YW, Kim D, Jung N |title=Gadd45 family proteins are coactivators of nuclear hormone receptors. |journal=Biochem. Biophys. Res. Commun. |volume=272 |issue= 1 |pages= 193–8 |year= 2000 |pmid= 10872826 |doi=10.1006/bbrc.2000.2760 |display-authors=etal}}
*{{cite journal  | author=Zhan Q, Antinore MJ, Wang XW, ''et al.'' |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 |year= 1999 |pmid= 10362260 |doi= 10.1038/sj.onc.1202667 }}
*{{cite journal  |vauthors=Zhao H, Jin S, Antinore MJ |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 |year= 2000 |pmid= 10912791 |doi= 10.1006/excr.2000.4906 |display-authors=etal}}
*{{cite journal  | author=Jin S, Antinore MJ, Lung FD, ''et al.'' |title=The GADD45 inhibition of Cdc2 kinase correlates with GADD45-mediated growth suppression. |journal=J. Biol. Chem. |volume=275 |issue= 22 |pages= 16602-8 |year= 2000 |pmid= 10747892 |doi= 10.1074/jbc.M000284200 }}
*{{cite journal  |vauthors=Yang Q, Manicone A, Coursen JD |title=Identification of a functional domain in a GADD45-mediated G2/M checkpoint. |journal=J. Biol. Chem. |volume=275 |issue= 47 |pages= 36892–8 |year= 2001 |pmid= 10973963 |doi= 10.1074/jbc.M005319200 |display-authors=etal}}
*{{cite journal  | author=Vairapandi M, Azam N, Balliet AG, ''et al.'' |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 |year= 2000 |pmid= 10828065 |doi=  }}
*{{cite journal  |vauthors=Hartley JL, Temple GF, Brasch MA |title=DNA cloning using in vitro site-specific recombination. |journal=Genome Res. |volume=10 |issue= 11 |pages= 1788–95 |year= 2001 |pmid= 11076863 |doi=10.1101/gr.143000  | pmc=310948 }}
*{{cite journal  | author=Yi YW, Kim D, Jung N, ''et al.'' |title=Gadd45 family proteins are coactivators of nuclear hormone receptors. |journal=Biochem. Biophys. Res. Commun. |volume=272 |issue= 1 |pages= 193-8 |year= 2000 |pmid= 10872826 |doi=  }}
*{{cite journal  |vauthors=Kovalsky O, Lung FD, Roller PP, Fornace AJ |title=Oligomerization of human Gadd45a protein. |journal=J. Biol. Chem. |volume=276 |issue= 42 |pages= 39330–9 |year= 2001 |pmid= 11498536 |doi= 10.1074/jbc.M105115200 }}
*{{cite journal  | author=Zhao H, Jin S, Antinore MJ, ''et al.'' |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 |year= 2000 |pmid= 10912791 |doi= 10.1006/excr.2000.4906 }}
*{{cite journal  | author=Yang Q, Manicone A, Coursen JD, ''et al.'' |title=Identification of a functional domain in a GADD45-mediated G2/M checkpoint. |journal=J. Biol. Chem. |volume=275 |issue= 47 |pages= 36892-8 |year= 2001 |pmid= 10973963 |doi= 10.1074/jbc.M005319200 }}
*{{cite journal  | author=Hartley JL, Temple GF, Brasch MA |title=DNA cloning using in vitro site-specific recombination. |journal=Genome Res. |volume=10 |issue= 11 |pages= 1788-95 |year= 2001 |pmid= 11076863 |doi=  }}
*{{cite journal  | author=Kovalsky O, Lung FD, Roller PP, Fornace AJ |title=Oligomerization of human Gadd45a protein. |journal=J. Biol. Chem. |volume=276 |issue= 42 |pages= 39330-9 |year= 2001 |pmid= 11498536 |doi= 10.1074/jbc.M105115200 }}
}}
{{refend}}
{{refend}}
{{protein-stub}}
{{WikiDoc Sources}}

Revision as of 01:41, 27 October 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
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View/Edit Human

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

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

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

GADD45A has been shown to interact with:

See also

References

  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. ↑ 3.0 3.1 "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. ↑ 5.0 5.1 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. ↑ 6.0 6.1 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. ↑ 8.0 8.1 8.2 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. ↑ 9.0 9.1 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

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