Regulation of the mTOR Pathway by a Novel Rheb Binding Protein BNIP3
Abstract
Uncontrolled mTOR activation is a major contributing factor to the pathogenesis of TSC. mTOR is known to be regulated by a wide range of signals such hypoxia. The major goal of this project is to determine mTOR regulation by hypoxia. We proposed to focus on BNIP3 which is a Rheb interacting protein in mTOR regulation in response to hypoxia. Our goals outlined in the original proposal have been successfully completed. We confirmed that BNIP3 is indeed a Rheb interaction protein under physiological conditions. We demonstrate that BNIP3 plays a critical role in hypoxia-induced mTOR inhibition. Furthermore we found that BNIP3 itself has a growth inhibitory activity and inactivation of BNIP3 promotes cell growth in vitro and tumor growth in vivo. Our observation reveals an important mechanism of cell growth regulation by hypoxia. Our results also indicate potential therapeutic target for TSC disease which has a high level of mTOR and Rheb activation. Activation BNIP3 may inhibit Rheb and mTOR in TSC mutant cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2008
- Accession Number
- ADA486638
Entities
People
- Kun-liang Guan
Organizations
- University of Michigan