Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:FBXW7-mediated degradation of CCDC6 is impaired by ATM during DNA damage response in lung cancer cells. 2310 47