| First Author | Cam H | Year | 2010 |
| Journal | Mol Cell | Volume | 40 |
| Issue | 4 | Pages | 509-20 |
| PubMed ID | 21095582 | Mgi Jnum | J:166999 |
| Mgi Id | MGI:4866964 | Doi | 10.1016/j.molcel.2010.10.030 |
| Citation | Cam H, et al. (2010) mTORC1 signaling under hypoxic conditions is controlled by ATM-dependent phosphorylation of HIF-1alpha. Mol Cell 40(4):509-20 |
| abstractText | The mTOR complex-1 (mTORC1) coordinates cell growth and metabolism, acting as a restriction point under stress conditions such as low oxygen tension (hypoxia). Hypoxia suppresses mTORC1 signaling. However, the signals by which hypoxia suppresses mTORC1 are only partially understood, and a direct link between hypoxia-driven physiological stress and the regulation of mTORC1 signaling is unknown. Here we show that hypoxia results in ataxia telangiectasia mutated (ATM)-dependent phosphorylation of hypoxia-inducible factor 1-alpha (HIF-1alpha) on serine(696) and mediates downregulation of mTORC1 signaling. Deregulation of these pathways in pediatric solid tumor xenografts suggests a link between mTORC1 dysregulation and solid tumor development and points to an important role for hypoxic regulation of mTORC1 activity in tumor development. |
