FBXW7-mediated degradation of CCDC6 is impaired by ATM during DNA damage response in lung cancer cells
| Autor: | Zhao JunGang, Tang Jun, Ren KaiMing, Men WanFu |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Threonine
Proteasome Endopeptidase Complex F-Box-WD Repeat-Containing Protein 7 Lung Neoplasms DNA damage Ubiquitin-Protein Ligases Proteolysis Biophysics Cell Cycle Proteins Ataxia Telangiectasia Mutated Proteins Protein Serine-Threonine Kinases Bioinformatics Proto-Oncogene Mas Biochemistry FBXW7 Structural Biology Cell Line Tumor Genetics medicine Humans Phosphorylation Lung cancer Molecular Biology biology Oncogene medicine.diagnostic_test Ubiquitin F-Box Proteins Tumor Suppressor Proteins Cell Biology medicine.disease Ubiquitin ligase DNA-Binding Proteins Cytoskeletal Proteins CCDC6 Cell culture ATM biology.protein Cancer research Lung cancer cell DNA Damage |
| Zdroj: | FEBS Letters. 586:4257-4263 |
| ISSN: | 0014-5793 |
| Popis: | CCDC6 is rearranged in approximately 20% of papillary thyroid carcinomas and some lung cancers participating in the formation of PTC1/ret proto-oncogene oncogene. CCDC6 is involved in the cellular response to DNA damage and is stabilized by ATM-mediated phosphorylation at Thr434. However, the E3 ligase that targets CCDC6 for destruction is unknown. Here, we show that FBXW7 interacts with and targets CCDC6 for ubiquitin-mediated proteasomal degradation. Moreover, FBXW7-mediated CCDC6 degradation is impaired in response to DNA damage. Mechanistically, phosphorylation of CCDC6 at Thr434 by ATM during DNA damage response prevents FBXW6-CCDC6 interaction and FBXW7-mediated CCDC6 degradation. Our results suggest that the involvement of FBXW7 in targeting CCDC6 for destruction will be useful for the establishment of new therapeutic approaches for cancer treatment.Structured summary of protein interactionsFBXW7 physically interacts with CCDC6 by anti bait coimmunoprecipitation (View Interaction: 1, 2)FBXW7 physically interacts with CCDC6 and CUL1 by anti tag coimmunoprecipitation (View Interaction: 1, 2)FBXW7 physically interacts with CCDC6 by anti tag coimmunoprecipitation (View Interaction: 1, 2, 3, 4, 5)CCDC6 physically interacts with SKP1 and CUL1 by anti bait coimmunoprecipitation (View interaction)FBXO6 physically interacts with CUL1 by anti tag coimmunoprecipitation (View interaction)FBXW2 physically interacts with CUL1 by anti tag coimmunoprecipitation (View interaction)FBXO4 physically interacts with CUL1 by anti tag coimmunoprecipitation (View interaction) |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text