Activation of cyclin D1 expression by the ERK5 cascade
| Autor: | Alexandre Philips, Roseann Mulloy, Sara Salinas, Robert A. Hipskind |
|---|---|
| Přispěvatelé: | Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM) |
| Rok vydání: | 2003 |
| Předmět: |
Cancer Research
Cyclin E Transcription Genetic Cyclin D Cyclin A Cyclin B Breast Neoplasms Genetic Tumor Cells 03 medical and health sciences 0302 clinical medicine Cyclin D1 Cyclin-dependent kinase Genetics Tumor Cells Cultured Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Promoter Regions Genetic Molecular Biology Mitogen-Activated Protein Kinase 7 030304 developmental biology Mitogen-Activated Protein Kinase 1 0303 health sciences Cultured Mitogen-Activated Protein Kinase 3 biology Gene Expression Regulation Neoplastic Kinetics 030220 oncology & carcinogenesis biology.protein Cancer research Cyclin-dependent kinase complex Female Neoplastic/*physiology Humans Kinetics Mitogen-Activated Protein Kinase 1/metabolism Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinase 7 Mitogen-Activated Protein Kinases/*metabolism Promoter Regions (Genetics) Transcription Mitogen-Activated Protein Kinases Breast Neoplasms Cyclin D1/biosynthesis/*genetics Female Gene Expression Regulation Cyclin A2 |
| Zdroj: | Oncogene Oncogene, Nature Publishing Group, 2003, 22 (35), pp.5387--98. ⟨10.1038/sj.onc.1206839⟩ |
| ISSN: | 0950-9232 1476-5594 |
| DOI: | 10.1038/sj.onc.1206839⟩ |
| Popis: | Transcriptional activation of the cyclin D1 gene is a key step in cell proliferation. Accordingly, cyclin D1 overexpression is frequently an early step in neoplastic transformation, particularly in mammary epithelium. Numerous studies have linked elevated cyclin D1 promoter activity to a sustained activation of the ERK1/2 cascade. Here we show that the ERK5 cascade, a distinct mitogen-induced MAPK pathway, can also drive cyclin D1 expression. In CCL39 cells, serum induces a strong, prolonged peak of ERK1/2 and ERK5 phosphorylation, and subsequently elevates cyclin D1 mRNA and protein levels. Overexpression of constitutively active MEK5 and wt ERK5 induces a cyclin D1 reporter gene (D1 -973-luciferase) at least as well as constitutively active MEK1. Activation is blocked by kinase-dead mutants of ERK5 and ERK2, respectively. Mutation of the CRE at -50 in the cyclin D1 promoter decreases activation by the ERK5 but not the ERK1/2 cascade. Importantly, expression of kinase-dead ERK5 diminishes endogenous cyclin D1 protein induction by serum in CCL39 cells and the breast cancer cell lines MCF-7 and HS579. These data identify the cyclin D1 gene as a novel target of the ERK5 cascade, an observation with important implications in cancers involving cyclin D1 deregulation. |
| Databáze: | OpenAIRE |
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