GRK2-Dependent HuR Phosphorylation Regulates HIF1α Activation under Hypoxia or Adrenergic Stress
| Autor: | Federico Mayor, Verónica Rivas, Petronila Penela, Ángela Albitre, Vanesa Lafarga, Paula Ramos, Susana Rojo Berciano, María L. Martínez-Chantar, Olga Tapia, Clara Reglero |
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| Přispěvatelé: | Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Fundacion Ramon Areces, Comunidad de Madrid, UAM. Departamento de Biología Molecular, Instituto de Salud Carlos III - ISCIII, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fundación Ramón Areces, Universidad de Cantabria |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Adrenergic mRNA regulation Gene Protein Phosphorylation 0302 clinical medicine Breast cancer β-adrenergic signaling HIF1α Receptor Hypoxia biology [beta]-Adrenergic Signaling Kinase Chemistry BREAST-CANCER CELLS HuR Gene HIF1[alfa] lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Biología y Biomedicina / Biología VEGF Cell biology MCF-7 Cell Line Oncology 030220 oncology & carcinogenesis Phosphorylation HuR medicine.symptom Protein Binding GRK2 Gene HeLa Cell Line GRK2 lcsh:RC254-282 Article 03 medical and health sciences breast cancer Downregulation and upregulation medicine HIF1 alpha Epithelium Cell hypoxia Beta adrenergic receptor kinase Hypoxia (medical) 030104 developmental biology Cancer cell biology.protein beta-adrenergic signaling nucleocytoplasmic shuttling |
| Zdroj: | Repisalud Instituto de Salud Carlos III (ISCIII) Cancers Volume 12 Issue 5 Cancers, Vol 12, Iss 1216, p 1216 (2020) Biblos-e Archivo. Repositorio Institucional de la UAM instname Digital.CSIC. Repositorio Institucional del CSIC Cancers (Basel) . 2020 May 13;12(5):1216 UCrea Repositorio Abierto de la Universidad de Cantabria Universidad de Cantabria (UC) |
| Popis: | Adaptation to hypoxia is a common feature in solid tumors orchestrated by oxygen-dependent and independent upregulation of the hypoxia-inducible factor-1&alpha (HIF-1&alpha ). 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-1&alpha 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-1&alpha mRNA in hypoxic Hela cells. Interestingly, enhanced GRK2 and HuR expression correlate in luminal breast cancer patients. GRK2 also promotes the HuR/HIF-1&alpha axis and VEGF-C accumulation in normoxic MCF7 breast luminal cancer cells and is required for the induction of HuR/HIF1-&alpha in response to adrenergic stress. Our results point to a relevant role of the GRK2/HuR/HIF-1&alpha module in the adaptation of malignant cells to tumor microenvironment-related stresses. |
| Databáze: | OpenAIRE |
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