Bnip3 mediates the hypoxia-induced inhibition on mammalian target of rapamycin by interacting with Rheb. J Biol Chem 2007 Dec 07;282(49):35803-13
Date
10/12/2007Pubmed ID
17928295DOI
10.1074/jbc.M705231200Scopus ID
2-s2.0-37248999267 (requires institutional sign-in at Scopus site) 239 CitationsAbstract
The mammalian target of rapamycin (mTOR) is a central controller of cell growth, and it regulates translation, cell size, cell viability, and cell morphology. mTOR integrates a wide range of extracellular and intracellular signals, including growth factors, nutrients, energy levels, and stress conditions. Rheb, a Ras-related small GTPase, is a key upstream activator of mTOR. In this study, we found that Bnip3, a hypoxia-inducible Bcl-2 homology 3 domain-containing protein, directly binds Rheb and inhibits the mTOR pathway. Bnip3 decreases Rheb GTP levels in a manner depending on the binding to Rheb and the presence of the N-terminal domain. Both knockdown and overexpression experiments show that Bnip3 plays an important role in mTOR inactivation in response to hypoxia. Moreover, Bnip3 inhibits cell growth in vivo by suppressing the mTOR pathway. These observations demonstrate that Bnip3 mediates the inhibition of the mTOR pathway in response to hypoxia.
Author List
Li Y, Wang Y, Kim E, Beemiller P, Wang CY, Swanson J, You M, Guan KLMESH terms used to index this publication - Major topics in bold
AnimalsCell Hypoxia
Cell Line
Cell Size
Cell Survival
Humans
Membrane Proteins
Mice
Mice, Nude
Monomeric GTP-Binding Proteins
Neuropeptides
Protein Biosynthesis
Protein Kinases
Protein Structure, Tertiary
Proto-Oncogene Proteins
Ras Homolog Enriched in Brain Protein
Signal Transduction
TOR Serine-Threonine Kinases
