Genomes and Genes
Brendan D Manning
Affiliation: Harvard University
- Hoxhaj G, Hughes Hallett J, Timson R, Ilagan E, Yuan M, Asara J, et al. The mTORC1 Signaling Network Senses Changes in Cellular Purine Nucleotide Levels. Cell Rep. 2017;21:1331-1346 pubmed publisher..Our findings suggest that nucleotide sensing, like amino acid sensing, enables mTORC1 to tightly coordinate nutrient availability with the synthesis of macromolecules, such as protein and nucleic acids, produced from those nutrients. ..
- Manning B, Logsdon M, Lipovsky A, Abbott D, Kwiatkowski D, Cantley L. Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2. Genes Dev. 2005;19:1773-8 pubmed..This study demonstrates that attenuation of the PI3K-Akt pathway in tumors lacking TSC2 contributes to their benign nature. ..
- Menon S, Dibble C, Talbott G, Hoxhaj G, Valvezan A, Takahashi H, et al. Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome. Cell. 2014;156:771-85 pubmed publisher..These findings provide a unifying mechanism by which independent pathways affecting the spatial recruitment of mTORC1 and the TSC complex to Rheb at the lysosomal surface serve to integrate diverse growth signals. ..
- Valvezan A, Turner M, Belaid A, Lam H, Miller S, McNamara M, et al. mTORC1 Couples Nucleotide Synthesis to Nucleotide Demand Resulting in a Targetable Metabolic Vulnerability. Cancer Cell. 2017;32:624-638.e5 pubmed publisher..These findings reveal a metabolic vulnerability downstream of mTORC1 triggered by anabolic imbalance. ..
- Kelsey I, Zbinden M, Byles V, Torrence M, Manning B. mTORC1 suppresses PIM3 expression via miR-33 encoded by the SREBP loci. Sci Rep. 2017;7:16112 pubmed publisher..These results demonstrate that PIM3 is induced upon mTORC1 inhibition, with potential implications for the effects of mTORC1 inhibitors in TSC, cancers, and the many other disease settings influenced by aberrant mTORC1 signaling. ..