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- Title
FBXW7-mediated degradation of CCDC6 is impaired by ATM during DNA damage response in lung cancer cells
- Authors
JunGang, Zhao; Jun, Tang; WanFu, Men; KaiMing, Ren
- Abstract
Abstract: 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 interactions: FBXW7 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 )
- Subjects
LUNG cancer; DNA damage; PROTEIN-protein interactions; CANCER treatment; THYROID diseases; PROTO-oncogenes
- Publication
FEBS Letters, 2012, Vol 586, Issue 24, p4257
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2012.10.029