Delayed activation of insulin-like growth factor-1 receptor/Src/MAPK/Egr-1 signaling regulates clusterin expression, a pro-survival factor
| Autor: | Shinako Araki, Eva Cataldo, David A. Boothman, Konstantin Leskov, Lindsey D. Mayo, Meghan Beman, Tracy Criswell |
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| Rok vydání: | 2005 |
| Předmět: |
MAPK/ERK pathway
Cell Survival MAP Kinase Signaling System medicine.medical_treatment Biology Biochemistry Immediate-Early Proteins Receptor IGF Type 1 Gene product Insulin-like growth factor Cell Line Tumor Radiation Ionizing medicine Humans RNA Small Interfering Receptor Promoter Regions Genetic Molecular Biology Transcription factor Early Growth Response Protein 1 Glycoproteins Clusterin Cell Biology Cell biology DNA-Binding Proteins Enzyme Activation ErbB Receptors src-Family Kinases Gene Expression Regulation biology.protein Signal transduction Mitogen-Activated Protein Kinases Proto-oncogene tyrosine-protein kinase Src Molecular Chaperones Transcription Factors |
| Zdroj: | The Journal of biological chemistry. 280(14) |
| ISSN: | 0021-9258 |
| Popis: | Secretory clusterin protein (sCLU) is a general genotoxic stress-induced, pro-survival gene product implicated in aging, obesity, heart disease, and cancer. However, the regulatory signal transduction processes that control sCLU expression remain undefined. Here, we report that induction of sCLU is delayed, peaking 72 h after low doses of ionizing radiation, and is dependent on the up-regulation of insulin-like growth factor-1 as well as phosphorylation-dependent activation of its receptor (IGF-1 and IGF-1R, respectively). Activated IGF-1R then stimulates the downstream Src-Mek-Erk signal transduction cascade to ultimately transactivate the early growth response-1 (Egr-1) transcription factor, required for sCLU expression. Thus, ionizing radiation exposure causes stress-induced activation of IGF-1R-Src-Mek-Erk-Egr-1 signaling that regulates the sCLU pro-survival cascade pathway, important for radiation resistance in cancer therapy. |
| Databáze: | OpenAIRE |
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