English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/24501
Compartir / Impacto:
Estadísticas
Add this article to your Mendeley library MendeleyBASE
Citado 31 veces en Web of Knowledge®  |  Ver citas en Google académico
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Título

The COOH-Terminal Domain of Wild-Type Cot Regulates Its Stability and Kinase Specific Activity

AutorGándara, Maria Luisa; López-Larrubia, Pilar ; Hernando, Raquel; Castaño, José G.; Alemany, Susana
Fecha de publicaciónoct-2003
EditorAmerican Society for Microbiology
CitaciónMolecular and Cellular Biology 23(20): 7377-7390 (2003)
ResumenCot, initially identified as an oncogene in a truncated form, is a mitogen-activated protein kinase kinase kinase implicated in cellular activation and proliferation. Here, we show that this truncation of Cot results in a 10-fold increase in its overall kinase activity through two different mechanisms. Truncated Cot protein exhibits a lower turnover rate (half-life, 95 min) than wild-type Cot (half-life, 35 min). The degradation of wild-type and truncated Cot can be specifically inhibited by proteasome inhibitors in situ. The 20S proteasome also degrades wild-type Cot more efficiently than the truncated protein. Furthermore, the amino acid 435 to 457 region within the wild-type Cot COOH-terminal domain confers instability when transferred to the yellow fluorescent protein and targets this fusion protein to degradation via the proteasome. On the other hand, the kinase specific activity of wild-type Cot is 3.8-fold lower than that of truncated Cot, and it appears that the last 43 amino acids of the wild-type Cot COOH-terminal domain are those responsible for this inhibition of kinase activity. In conclusion, these data demonstrate that the oncogenic activity of truncated Cot is the result of its prolonged half-life and its higher kinase specific activity with respect to wild-type Cot.
Descripción14 pages, 9 figures.
Versión del editorhttp://dx.doi.org/10.1128/MCB.23.20.7377-7390.2003
URIhttp://hdl.handle.net/10261/24501
DOI10.1128/MCB.23.20.7377-7390.2003
ISSN0270-7306
Aparece en las colecciones: (IIBM) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
7377.pdf641,27 kBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 



NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.