|
|
ReportsFBXW7 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.
1 Cancer Research Institute, University of California at San Francisco, 2340 Sutter Street, San Francisco, CA 94143, USA.
2 Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, CA 94143, USA. * These authors contributed equally to this work.
The editors suggest the following Related Resources on Science sites:In Science Signaling
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
|
To whom correspondence should be addressed. E-mail: Science. ISSN 0036-8075 (print), 1095-9203 (online)
News | Science Journals | Careers | Blogs and Communities | Multimedia | Collections | Help | Site Map | RSS
Subscribe | Feedback | Privacy / Legal | About Us | Advertise With Us | Contact Us
© 2008 American Association for the Advancement of Science. All Rights Reserved.
AAAS is a partner of HINARI, AGORA, PatientInform, CrossRef, and COUNTER.
You have reached the bottom of the page. Back to top