Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/7124
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | p53 stabilization and accumulation induced by human vaccinia-related kinase 1 |
Autor: | Vega, Francisco M. CSIC ORCID; Sevilla Hernández, Ana CSIC ORCID; Lazo, Pedro A. CSIC ORCID | Palabras clave: | VRK1 p53 |
Fecha de publicación: | 2004 | Citación: | Molecular and Cellular Biology 24(23): 10366-10389 (2004) | Resumen: | Variations in intracellular levels of p53 regulate many cellular functions and determine tumor susceptibility. Major mechanisms modulating p53 levels include phosphorylation and interaction of p53 with specific ubiquitin ligases that promote its degradation. N-terminal phosphorylation regulates the interaction of p53 with several regulatory molecules. Vaccinia-related kinase 1 (VRK1) is the prototype of a new Ser-Thr kinase family in the human kinome. VRK1 is located in the nucleus outside the nucleolus. Overexpression of VRK1 increases the stability of p53 by a posttranslational mechanism leading to its accumulation by a mechanism independent of the Chk2 kinase. Catalytically inactive VRK1 protein (a K179E mutant) does not induce p53 accumulation. VRK1 phosphorylates human p53 in Thr18 and disrupts p53-Mdm2 interaction in vitro, although a significant decrease in p53 ubiquitination by Mdm2 in vivo was not detected. VRK1 kinase does not phosphorylate Mdm2. VRK1-mediated p53 stabilization was also detected in Mdm2 / cells. VRK1 also has an additive effect with MdmX or p300 to stabilize p53, and p300 coactivation and acetylation of p53 is enhanced by VRK1. The p53 stabilized by VRK1 is transcriptionally active. Suppression of VRK1 expression by specific small interfering RNA provokes several defects in proliferation, situating the protein in the regulation of this process. VRK1 might function as a switch controlling the proteins that interact with p53 and thus modifying its stability and activity. We propose VRK1 as the first step in a new pathway regulating p53 activity during cell proliferation. | Versión del editor: | http://dx.doi.org/10.1128/MCB.24.23.10366-10380.2004 | URI: | http://hdl.handle.net/10261/7124 | DOI: | 10.1128/MCB.24.23.10366-10380.2004 | ISSN: | 0270-7306 |
Aparece en las colecciones: | (IBMCC) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
p53 Stabilization.pdf | 1,13 MB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
PubMed Central
Citations
71
checked on 19-abr-2024
SCOPUSTM
Citations
112
checked on 23-abr-2024
WEB OF SCIENCETM
Citations
107
checked on 25-feb-2024
Page view(s)
375
checked on 23-abr-2024
Download(s)
264
checked on 23-abr-2024
Google ScholarTM
Check
Altmetric
Altmetric
Artículos relacionados:
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.