FBXW7 targets mTOR for degradation and cooperates with PTEN in tumor suppression.
The enzyme mTOR (mammalian target of rapamycin) is a major target for therapeutic intervention to treat many human diseases, including cancer, but very little is known about the processes that control levels of mTOR protein. Here, we show that mTOR is targeted for ubiquitination and consequent degradation by binding to ... the tumor suppressor protein FBXW7. Human breast cancer cell lines and primary tumors showed a reciprocal relation between loss of FBXW7 and deletion or mutation of PTEN (phosphatase and tensin homolog), which also activates mTOR. Tumor cell lines harboring deletions or mutations in FBXW7 are particularly sensitive to rapamycin treatment, which suggests that loss of FBXW7 may be a biomarker for human cancers susceptible to treatment with inhibitors of the mTOR pathway.
Mesh Terms:
Animals, Breast Neoplasms, Cell Cycle Proteins, Cell Line, Cell Line, Tumor, F-Box Proteins, Gene Deletion, Gene Dosage, Gene Silencing, Genes, Tumor Suppressor, Humans, Mice, Mice, Nude, Mutation, Neoplasm Transplantation, PTEN Phosphohydrolase, Phosphorylation, Protein Binding, Protein Kinases, Proto-Oncogene Proteins c-akt, Signal Transduction, Sirolimus, Transfection, Tumor Suppressor Proteins, Ubiquitin-Protein Ligases, Ubiquitination
Animals, Breast Neoplasms, Cell Cycle Proteins, Cell Line, Cell Line, Tumor, F-Box Proteins, Gene Deletion, Gene Dosage, Gene Silencing, Genes, Tumor Suppressor, Humans, Mice, Mice, Nude, Mutation, Neoplasm Transplantation, PTEN Phosphohydrolase, Phosphorylation, Protein Binding, Protein Kinases, Proto-Oncogene Proteins c-akt, Signal Transduction, Sirolimus, Transfection, Tumor Suppressor Proteins, Ubiquitin-Protein Ligases, Ubiquitination
Science
Date: Sep. 12, 2008
PubMed ID: 18787170
View in: Pubmed Google Scholar
Download Curated Data For This Publication
85969
Switch View:
- Interactions 1