English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/124295
COMPARTIR / IMPACTO:
Estadísticas
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
Título

Interaction between PARP-1 and HIF-2 in the hypoxic response

AutorGonzález-Flores, Ariannys; Aguilar-Quesada, Rocío; Rodríguez-Lara, María Isabel; López-Jiménez, L.; López-Rodríguez, M.; Peralta, Andreína; Villar, Diego; Peso, Luis del; Oliver, Francisco Javier
Fecha de publicación2014
EditorNature Publishing Group
CitaciónOncogene 33(7): 891-898 (2014)
ResumenHypoxia-inducible factors (HIFs) mediate the transcriptional adaptation of hypoxic cells. The extensive transcriptional programm regulated by HIFs involves the induction of genes controlling angiogenesis, cellular metabolism, cell growth, metastasis, apoptosis, extracellular matrix remodeling and others. HIF is a heterodimer of HIF- and HIF-β subunits. In addition to HIF-1, HIF-2 has evolved as an isoform that contributes differently to the hypoxic adaptation by performing non-redundant functions. Poly (ADP-ribose) polymerase-1 (PARP-1) is a nuclear protein involved in the control of DNA repair and gene transcription by modulating chromatin structure and acting as part of gene-specific enhancer/promoter-binding complexes. Previous results have shown that PARP-1 regulates HIF-1 activity. In this study, we focused on the cross-talk between HIF-2 and PARP-1. By using different approaches to suppress PARP-1, we show that HIF-2 mRNA expression, protein levels and HIF-2-dependent gene expression, such as ANGPTL4 and erythropoietin (EPO), are regulated by PARP-1. This regulation occurs at both the transcriptional and post-trancriptional level. We also show a complex formation between HIF-2 with PARP-1. This complex is sensitive to PARP inhibition and seems to protect against the von Hippel-Lindau-dependent HIF-2 degradation. Finally, we show that parp-1-/-mice display a significant reduction in the circulating hypoxia-induced EPO levels, number of red cells and hemoglobin concentration. Altogether, these results reveal a complex functional interaction between PARP-1 and the HIF system and suggest that PARP-1 is involved in the fine tuning of the HIF-mediated hypoxic response in vivo.
Descripciónet al.
URIhttp://hdl.handle.net/10261/124295
DOI10.1038/onc.2013.9
Identificadoresdoi: 10.1038/onc.2013.9
issn: 0950-9232
e-issn: 1476-5594
Aparece en las colecciones: (IIBM) Artículos
(IPBLN) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
accesoRestringido.pdf15,38 kBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 

Artículos relacionados:


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