Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/212546
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | GRK2-Dependent HuR Phosphorylation Regulates HIF1α Activation under Hypoxia or Adrenergic Stress |
Autor: | Reglero, Clara CSIC ORCID; Lafarga, Vanesa CSIC ORCID; Rivas, Verónica CSIC ORCID; Albitre, Ángela; Ramos, Paula CSIC ORCID; Berciano, Susana R.; Tapia, Olga; Martínez-Chantar, María Luz CSIC ORCID; Mayor Menéndez, Federico CSIC ORCID; Penela, Petronila CSIC ORCID | Palabras clave: | Hypoxia β-adrenergic signaling Breast cancer mRNA regulation Nucleocytoplasmic shuttling GRK2 HuR HIF1α VEGF |
Fecha de publicación: | 2020 | Editor: | Multidisciplinary Digital Publishing Institute | Citación: | Cancers 12(5): 1216 (2020) | Resumen: | Adaptation to hypoxia is a common feature in solid tumors orchestrated by oxygen-dependent and independent upregulation of the hypoxia-inducible factor-1α (HIF-1α). We unveiled that G protein-coupled receptor kinase (GRK2), known to be overexpressed in certain tumors, fosters this hypoxic pathway via phosphorylation of the mRNA-binding protein HuR, a central HIF-1α modulator. GRK2-mediated HuR phosphorylation increases the total levels and cytoplasmic shuttling of HuR in response to hypoxia, and GRK2-phosphodefective HuR mutants show defective cytosolic accumulation and lower binding to HIF-1α mRNA in hypoxic Hela cells. Interestingly, enhanced GRK2 and HuR expression correlate in luminal breast cancer patients. GRK2 also promotes the HuR/HIF-1α axis and VEGF-C accumulation in normoxic MCF7 breast luminal cancer cells and is required for the induction of HuR/HIF1-α in response to adrenergic stress. Our results point to a relevant role of the GRK2/HuR/HIF-1α module in the adaptation of malignant cells to tumor microenvironment-related stresses. | Descripción: | © 2020 by the authors. | Versión del editor: | https://doi.org/10.3390/cancers12051216 | URI: | http://hdl.handle.net/10261/212546 | DOI: | 10.3390/cancers12051216 | E-ISSN: | 2072-6694 |
Aparece en las colecciones: | (CBM) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
GRK2_Dependent_Reglero_Art2020.pdf | 3,44 MB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
PubMed Central
Citations
9
checked on 20-abr-2024
SCOPUSTM
Citations
14
checked on 23-abr-2024
WEB OF SCIENCETM
Citations
12
checked on 27-feb-2024
Page view(s)
147
checked on 23-abr-2024
Download(s)
217
checked on 23-abr-2024