Proteasome- and p38-dependent regulation of ERK3 expression
| Autor: | Peter Fürst, Johann Zimmermann, Nathalie Lamerant, Rita Grossenbacher |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
MAPK/ERK pathway
Proteasome Endopeptidase Complex MAP Kinase Signaling System p38 mitogen-activated protein kinases Lactacystin Biochemistry Gene Expression Regulation Enzymologic chemistry.chemical_compound Ubiquitin Multienzyme Complexes Heat shock protein Tumor Cells Cultured Humans Molecular Biology Transcription factor biology Cell Biology Molecular biology Cell biology Enzyme Activation Cysteine Endopeptidases Proteasome chemistry biology.protein Signal transduction Mitogen-Activated Protein Kinases |
| Zdroj: | The Journal of biological chemistry. 276(14) |
| ISSN: | 0021-9258 |
| Popis: | Proteasome inhibition leads to accumulation of transcription factors, heat shock proteins, cyclins, and other proteasome substrate proteins by blocking their proteolytic degradation. An increase in gene transcription upon proteasome inhibition was found for a group of proteins, including p21(WAF1/CIP1), ubiquitin, and transcription factors. In this study, we have demonstrated selective up-regulation of extracellular signal-regulated kinase 3 (ERK3) mRNA and protein expression upon treatment with peptide-based proteasome inhibitors or lactacystin. ERK3 is a family member of the mitogen-activated protein kinases (also called ERK) that are key mediators of signal transduction from the cell surface to the nucleus. ERK3 up-regulation is independent of the p53, Bcl2, and caspase 3 status of cells. p38 pathway kinase inhibitors prevent proteasome-dependent ERK3 induction and enhance the antiproliferative effect of proteasome inhibitors. MCF-7 cells expressing ERK3 ectopically show increased resistance toward proteasome inhibition. The results indicate that ERK3 expression is a consequence of p38 pathway activation and most probably represents an intracellular defense or rescue mechanism against cell stress and damage induced by proteasome inhibition. |
| Databáze: | OpenAIRE |
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