Differential Sensitivity of v-Myb and c-Myb to Wnt-1-induced Protein Degradation
| Autor: | Teruaki Nomura, Emi Ichikawa-Iwata, Shunsuke Ishii, Chie Kanei-Ishii, Jun Tanikawa |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Proto-Oncogene Mas
Biochemistry Mice Ubiquitin MYB Phosphorylation Glutathione Transferase chemistry.chemical_classification Kinase Wnt signaling pathway Amino acid Cell Transformation Neoplastic Plasmids Protein Binding Signal Transduction Chloramphenicol O-Acetyltransferase animal structures Blotting Western Wnt1 Protein Protein Serine-Threonine Kinases Biology Protein degradation Transfection Binding Competitive Models Biological Proto-Oncogene Proteins c-myb Leucine Cell Line Tumor Proto-Oncogene Proteins Two-Hybrid System Techniques Animals Humans Point Mutation Protein kinase A Molecular Biology Binding Sites Dose-Response Relationship Drug fungi DNA Cell Biology Molecular biology Oncogene Proteins v-myb Protein Structure Tertiary Wnt Proteins Gene Expression Regulation chemistry Mutation biology.protein Carrier Proteins |
| Zdroj: | Journal of Biological Chemistry. 279:44582-44589 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m407831200 |
| Popis: | Recently we have shown that the c-myb proto-oncogene product (c-Myb) is degraded in response to Wnt-1 signaling via the pathway involving TAK1 (transforming growth factor-beta-activated kinase), HIPK2 (homeodomain-interacting protein kinase 2), and NLK (Nemo-like kinase). NLK and HIPK2 bind directly to c-Myb, which results in the phosphorylation of c-Myb at multiple sites, followed by its ubiquitination and proteasome-dependent degradation. The v-myb gene carried by avian myeloblastosis virus has a transforming capacity, but the c-myb proto-oncogene does not. Here, we report that two characteristics of v-Myb make it relatively resistant to Wnt-1-induced protein degradation. First, HIPK2 binds with a lower affinity to the DNA-binding domain of v-Myb than to that of c-Myb. The mutations of three hydrophobic amino acids on the surface of the DNA-binding domain in v-Myb decrease the affinity to HIPK2. Second, a loss of multiple NLK phosphorylation sites by truncation of the C-terminal region of c-Myb increases its stability. Among 15 putative NLK phosphorylation sites in mouse c-Myb, the phosphorylation sites in the C-terminal region are more critical than other sites for Wnt-1-induced protein degradation. The relative resistance of v-Myb to Wnt-1-induced degradation may explain, at least in part, the differential transforming capacity of v-Myb versus c-Myb. |
| Databáze: | OpenAIRE |
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