English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/114000
Compartir / Impacto:
Estadísticas
Add this article to your Mendeley library MendeleyBASE
Citado 17 veces en Web of Knowledge®  |  Pub MebCentral Ver citas en PubMed Central  |  Ver citas en Google académico
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar otros formatos: Exportar EndNote (RIS)Exportar EndNote (RIS)Exportar EndNote (RIS)
Título

Mutual regulation between SIAH2 and DYRK2 controls hypoxic and genotoxic signaling pathways

Autor Pérez, Moisés; García-Limones, Carmen; Zapico, Inés; Marina, Anabel; Schmitz, M. Lienhard; Muñoz, Eduardo; Calzado, Marco A.
Palabras clave Ubiquitination
Phosphorylation
Hypoxia
DYRK2
SIAH2
Fecha de publicación 2012
EditorOxford University Press
Citación Journal of Molecular Cell Biology 4: 316- 330 (2012)
ResumenThe ubiquitin E3 ligase SIAH2 is an important regulator of the hypoxic response as it leads to the ubiquitin/proteasomal degradation of prolyl hydroxylases such as PHD3, which in turn increases the stability of hypoxia-inducible factor (HIF)-1α. In the present study, we identify the serine/threonine kinase DYRK2 as SIAH2 interaction partner that phosphorylates SIAH2 at five residues (Ser16, Thr26, Ser28, Ser68, and Thr119). Phosphomimetic and phospho-mutant forms of SIAH2 exhibit different subcellular localizations and consequently change in PHD3 degrading activity. Accordingly, phosphorylated SIAH2 is more active than the wild-type E3 ligase and shows an increased ability to trigger the HIF-1α-mediated transcriptional response and angiogenesis. We also found that SIAH2 knockdown increases DYRK2 stability, whereas SIAH2 expression facilitates DYRK2 polyubiquitination and degradation. Hypoxic conditions cause a SIAH2-dependent DYRK2 polyubiquitination and degradation which ultimately also results in an impaired SIAH2 phosphorylation. Similarly, DYRK2-mediated phosphorylation of p53 at Ser46 is impaired under hypoxic conditions, suggesting a molecular mechanism underlying chemotherapy resistance in solid tumors. © 2012 The Author (2012). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.
URI http://hdl.handle.net/10261/114000
DOI10.1093/jmcb/mjs047
Identificadoresdoi: 10.1093/jmcb/mjs047
issn: 1674-2788
Aparece en las colecciones: (CBM) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
accesoRestringido.pdf15,38 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.