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http://repositorio.pediatria.gob.mx:8180/handle/20.500.12103/2953| Título : | Allosteric interactions by p53 mRNA govern HDM2 E3 ubiquitin ligase specificity under different conditions |
| Creador: | Medina Medina I., |
| Nivel de acceso: | Open access |
| Palabras clave : | Regulación Alostérica Animales Proteínas de la Ataxia Telangiectasia Mutada - metabolismo Humanos Proteínas Nucleares - química Proteínas Nucleares - metabolismo Fosforilación Dominios Proteicos Desplegamiento Proteico Proteínas Proto-Oncogénicas - química Proteínas Proto-Oncogénicas - metabolismo Proteínas Proto-Oncogénicas c-mdm2 - química Proteínas Proto-Oncogénicas c-mdm2 - metabolismo ARN Mensajero - metabolismo Especificidad por Sustrato Proteína p53 Supresora de Tumor - genética Proteína p53 Supresora de Tumor - metabolismo Allosteric Regulation Animals Ataxia Telangiectasia Mutated Proteins - metabolism Humans Nuclear Proteins - chemistry Nuclear Proteins - metabolism Phosphorylation Protein Domains Protein Unfolding Proto-Oncogene Proteins - chemistry Proto-Oncogene Proteins - metabolism Proto-Oncogene Proteins c-mdm2 - chemistry Proto-Oncogene Proteins c-mdm2 - metabolism RNA, Messenger - metabolism Substrate Specificity Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism Sitios Alostéricos Proteínas de la Ataxia Telangiectasia Mutada Proteínas Nucleolares Proteínas mdm2 Proteína Supresora de Tumores p53 RNAm Especificidad por Sustrato Allosteric Site Ataxia Telangiectasia Mutated Proteins Nuclear Proteins Proto-Oncogene Proteins c-mdm2 umor Suppressor Protein p53 mRNA Substrate Specificity |
| Descripción : | HDM2 and HDMX are key negative regulatory factors of the p53 tumor suppressor under normal conditions by promoting its degradation or preventing its trans activity, respectively. It has more recently been shown that both proteins can also act as positive regulators of p53 afterDNAdamage. This involves phosphorylation byATMon serine residues HDM2(S395) and HDMX(S403), promoting their respective interaction with the p53 mRNA. However, the underlying molecular mechanisms of how these phosphorylation events switch HDM2 and HDMX from negative to positive regulators of p53 is not known. Our results show that these phosphorylation events reside within intrinsically disordered domains and change the conformation of the proteins. The modifications promote the exposition of N-terminal interfaces that support the formation of a new HDMX-HDM2 heterodimer independent of the C-terminal RING-RING interaction. The E3 ubiquitin ligase activity of this complex toward p53 is prevented by the p53 mRNA ligand but, interestingly, does not affect the capacity to ubiquitinate HDMX and HDM2. These results show how ATM-mediated modifications of HDMX and HDM2 switch HDM2 E3 ubiquitin ligase activity away from p53 but toward HDMX and itself and illustrate how the substrate specificity of HDM2 E3 ligase activity is regulated. © 2016, American Society for Microbiology. |
| Colaborador(es) u otros Autores: | García-Beltrán P. de la Mora-de la Mora I. Oria-Hernández J. Millot G. Fahraeus R. Reyes-Vivas H. Sampedro J.G. Olivares-Illana V. |
| Fecha de publicación : | 2016 |
| Tipo de publicación: | Artículo |
| Formato: | |
| Identificador del Recurso : | 10.1128/MCB.00113-16 |
| Fuente: | Molecular and Cellular Biology 36(15):2195 - 2205 |
| URI : | http://repositorio.pediatria.gob.mx:8180/handle/20.500.12103/2953 |
| Idioma: | eng |
| Aparece en las colecciones: | Artículos |
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