Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

FBXW7 targets mTOR for degradation and cooperates with PTEN in tumor suppression.

Science (New York, N.Y.) | Sep 12, 2008

http://www.ncbi.nlm.nih.gov/pubmed/18787170

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.

Pubmed ID: 18787170 RIS Download

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 | TOR Serine-Threonine Kinases | Transfection | Tumor Suppressor Proteins | Ubiquitin-Protein Ligases | Ubiquitination

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: R01 CA116481
  • Agency: NCI NIH HHS, Id: U01 CA084244
  • Agency: NCI NIH HHS, Id: U01 CA084244-08
  • Agency: NCI NIH HHS, Id: U01 CA084244-09
  • Agency: NCI NIH HHS, Id: U01 CA084244-10

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.