GADD45A
La proteína de arresto de crecimiento e inducible por daños en el ADN GADD45 alfa es una proteína que en humanos está codificada por el gen GADD45A.[1][2][3]
Función[editar]
Este gen es un miembro de un grupo de genes, los genes GADD45, cuyos niveles de transcripción aumentan luego de condiciones estresantes de detención de crecimiento y tratamiento con agentes que dañan el ADN (mutágenos). La transcripción inducida por el daño en el ADN de este gen está mediada por mecanismos dependientes e independientes de p53. La proteína codificada por este gen responde al estrés ambiental al mediar la activación de la vía p38/JNK a través de la quinasa MTK1/MEKK4.[3]
Aplicaciones[editar]
Se ha explotado el hecho de que la expresión de este gen sea un indicador de daño en el ADN para poner a punto una prueba in vitro de mutagenicidad, el ensayo GreenScreen HC de GADD45a-GFP.[4] Este ensayo consiste en una línea celular que se ha diseñado para que la expresión de GADD45A esté asociada a la expresión de la proteína verde fluorescente, que puede detectarse fácilmente. Para probar la mutagenicidad de una sustancia, se aplica a estas células y se mide la fluorescencia.
Interacciones[editar]
Se ha demostrado que GADD45A interactúa con:
- AURKA[5][5]
- Cdk1[6][7][8][9]
- CCNB1[6][9]
- GADD45GIP1[10]
- MAP3K4[11]
- P21[8][12] y
- PCNA[8][13][14][15][16]
Véase también[editar]
Referencias[editar]
- ↑ «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. March 1991. PMC 359769. PMID 1990262.
- ↑ «Analysis of the mammalian gadd45 gene and its response to DNA damage». J Biol Chem 268 (32): 24385-93. December 1993. PMID 8226988.
- ↑ a b «Entrez Gene: GADD45A growth arrest and DNA-damage-inducible, alpha».
- ↑ «The GADD45a-GFP GreenScreen HC assay». Methods Mol. Biol. 817: 231-50. 2012. PMID 22147576. doi:10.1007/978-1-61779-421-6_12.
- ↑ a b «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. July 2010. PMC 2903397. PMID 20460379. doi:10.1074/jbc.M109.069344.
- ↑ a b «Association with Cdc2 and inhibition of Cdc2/Cyclin B1 kinase activity by the p53-regulated protein Gadd45». Oncogene 18 (18): 2892-900. May 1999. PMID 10362260. doi:10.1038/sj.onc.1202667.
- ↑ «The GADD45 inhibition of Cdc2 kinase correlates with GADD45-mediated growth suppression». J. Biol. Chem. 275 (22): 16602-8. June 2000. PMID 10747892. doi:10.1074/jbc.M000284200.
- ↑ a b c «Identification of a functional domain in a GADD45-mediated G2/M checkpoint». J. Biol. Chem. 275 (47): 36892-8. November 2000. PMID 10973963. doi:10.1074/jbc.M005319200.
- ↑ a b «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. September 2002. PMID 12124778. doi:10.1002/jcp.10140.
- ↑ «CR6-interacting factor 1 interacts with Gadd45 family proteins and modulates the cell cycle». J. Biol. Chem. 278 (30): 28079-88. July 2003. PMID 12716909. doi:10.1074/jbc.M212835200.
- ↑ «A family of stress-inducible GADD45-like proteins mediate activation of the stress-responsive MTK1/MEKK4 MAPKKK». Cell 95 (4): 521-30. November 1998. PMID 9827804. doi:10.1016/s0092-8674(00)81619-0.
- ↑ «The central region of Gadd45 is required for its interaction with p21/WAF1». Exp. Cell Res. 258 (1): 92-100. July 2000. PMID 10912791. doi:10.1006/excr.2000.4906.
- ↑ «Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen». Science 266 (5189): 1376-80. November 1994. PMID 7973727. doi:10.1126/science.7973727.
- ↑ «Direct interaction of Gadd45 with PCNA and evidence for competitive interaction of Gadd45 and p21Waf1/Cip1 with PCNA». Oncogene 11 (10): 1931-7. November 1995. PMID 7478510.
- ↑ «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. June 2000. PMID 10828065. doi:10.1074/jbc.275.22.16810.
- ↑ «Characterisation of the interaction between PCNA and Gadd45». Oncogene 10 (12): 2427-33. June 1995. PMID 7784094.
Bibliografía[editar]
- 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 (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 (1995). «Characterisation of the interaction between PCNA and Gadd45.». Oncogene 10 (12): 2427-33. PMID 7784094.
- Carrier F, Smith ML, Bae I (1995). «Characterization of human Gadd45, a p53-regulated protein.». J. Biol. Chem. 269 (51): 32672-7. PMID 7798274.
- Smith ML, Chen IT, Zhan Q (1994). «Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen.». Science 266 (5189): 1376-80. PMID 7973727. doi:10.1126/science.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. PMID 9178907. doi:10.1038/sj.onc.1201072.
- 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. PMC 147798. PMID 9705499. doi:10.1093/nar/26.17.3925.
- 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. PMID 9827804. doi:10.1016/S0092-8674(00)81619-0.
- Carrier F, Georgel PT, Pourquier P (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 (1999). «Association with Cdc2 and inhibition of Cdc2/Cyclin B1 kinase activity by the p53-regulated protein Gadd45.». Oncogene 18 (18): 2892-900. PMID 10362260. doi:10.1038/sj.onc.1202667.
- Jin S, Antinore MJ, Lung FD (2000). «The GADD45 inhibition of Cdc2 kinase correlates with GADD45-mediated growth suppression.». J. Biol. Chem. 275 (22): 16602-8. PMID 10747892. doi:10.1074/jbc.M000284200.
- Vairapandi M, Azam N, Balliet AG (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. PMID 10828065. doi:10.1074/jbc.275.22.16810.
- Yi YW, Kim D, Jung N (2000). «Gadd45 family proteins are coactivators of nuclear hormone receptors.». Biochem. Biophys. Res. Commun. 272 (1): 193-8. PMID 10872826. doi:10.1006/bbrc.2000.2760.
- Zhao H, Jin S, Antinore MJ (2000). «The central region of Gadd45 is required for its interaction with p21/WAF1.». Exp. Cell Res. 258 (1): 92-100. PMID 10912791. doi:10.1006/excr.2000.4906.
- Yang Q, Manicone A, Coursen JD (2001). «Identification of a functional domain in a GADD45-mediated G2/M checkpoint.». J. Biol. Chem. 275 (47): 36892-8. PMID 10973963. doi:10.1074/jbc.M005319200.
- Hartley JL, Temple GF, Brasch MA (2001). «DNA cloning using in vitro site-specific recombination.». Genome Res. 10 (11): 1788-95. PMC 310948. PMID 11076863. doi:10.1101/gr.143000.
- Kovalsky O, Lung FD, Roller PP, Fornace AJ (2001). «Oligomerization of human Gadd45a protein.». J. Biol. Chem. 276 (42): 39330-9. PMID 11498536. doi:10.1074/jbc.M105115200.
