Suppression of MEK/ERK signalling by Myc: role of Bin-1
| Autor: | Joan F. Telfer, Dorothy H. Crouch, Jennifer Urquhart |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
MAPK/ERK pathway
MAP Kinase Signaling System medicine.medical_treatment Down-Regulation Apoptosis Nerve Tissue Proteins Chick Embryo Mitogen-activated protein kinase kinase Autocrine Communication Proto-Oncogene Proteins c-myc Mice Downregulation and upregulation Nitriles Butadienes medicine Animals Extracellular Signal-Regulated MAP Kinases Growth Substances Protein Kinase Inhibitors Cells Cultured Adaptor Proteins Signal Transducing Cell Nucleus Mitogen-Activated Protein Kinase Kinases Kinase Chemistry Tumor Suppressor Proteins Growth factor Cell Biology Protein Structure Tertiary Cell biology Cell Transformation Neoplastic |
| Zdroj: | Cellular Signalling. 17:701-708 |
| ISSN: | 0898-6568 |
| Popis: | We report for the first time that over-expression of Myc suppresses mitogen-activated ERK kinase (MEK)/extracellular regulated kinase (ERK) signalling in chick embryo fibroblasts (CEF). Myc does not interfere with individual components of the signalling cascade, since efficient signal propagation via MEK and ERK in Myc-infected CEF can be seen. However, using the Myc-binding domain (MBD) of Bin-1, which binds to and negatively regulates the activity of Myc, we selectively suppressed Myc-induced apoptosis, without affecting its transforming properties. This was accompanied by a restoration in MEK/ERK signalling, suggesting a critical role for this pathway in regulating apoptosis in these cells. This was also confirmed using a specific pharmacological inhibitor of MEK. Experiments with conditioned media suggest that over-expression of Myc may inhibit autocrine growth factor production, which can be restored by co-expression of MBD. Although the identity of the growth factor(s) is not known, we propose a feedback mechanism whereby Myc interferes with growth factor signalling. |
| Databáze: | OpenAIRE |
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