Now showing items 1-9 of 9

    • Coordinated regulation of protein synthesis and degradation by mTORC1 

      Zhang, Yinan; Nicholatos, Justin William; Dreier, John; Ricoult, Stephane Jean Hermann; Widenmaier, Scott Bradley; Hotamisligil, Gokhan S.; Kwiatkowski, David Joseph; Manning, Brendan D. (Springer Science and Business Media LLC, 2014-07-13)
      Eukaryotic cells coordinately control anabolic and catabolic processes to maintain cell and tissue homeostasis. Mechanistic target of rapamycin complex 1 (mTORC1) promotes nutrient-consuming anabolic processes, such as ...
    • Ex Vivo and in Vivo Stable Isotope Labelling of Central Carbon Metabolism and Related Pathways With Analysis by LC–MS/MS 

      Yuan, Min; Kremer, Daniel M.; Huang, He; Breitkopf, Susanne B.; Ben-Sahra, Issam; Manning, Brendan; Lyssiotis, Costas A.; Asara, John (Springer Science and Business Media LLC, 2019-02)
      Targeted tandem mass spectrometry (LC–MS/MS) has been extremely useful for profiling small molecules extracted from biological sources, such as cells, bodily fluids and tissues. Here, we present a protocol for analysing ...
    • mTORC1 Couples Nucleotide Synthesis to Nucleotide Demand Resulting in a Targetable Metabolic Vulnerability 

      Valvezan, Alexander J.; Turner, Marc; Belaid, Amine; Lam, Hilaire; Miller, Spencer K.; Mcnamara, Molly; Baglini, Christian; Housden, Benjamin; Perrimon, Norbert; Kwiatkowski, David; Asara, John; Henske, Elizabeth; Manning, Brendan (Elsevier BV, 2017-11-13)
      The mechanistic target of rapamycin complex 1 (mTORC1) supports proliferation through parallel induction of key anabolic processes, including protein, lipid, and nucleotide synthesis. We hypothesized that these processes ...
    • NF2/Merlin Is a Novel Negative Regulator of mTOR Complex 1, and Activation of mTORC1 Is Associated with Meningioma and Schwannoma Growth 

      James, Marianne; Han, S; Polizzano, Carolyn; Plotkin, Scott Randall; Manning, Brendan D.; Stemmer-Rachamimov, Anat; Gusella, James Francis; Ramesh, Vijaya (American Society for Microbiology, 2009)
      Inactivating mutations of the neurofibromatosis 2 (NF2) gene, NF2, result predominantly in benign neurological tumors, schwannomas and meningiomas, in humans; however, mutations in murine Nf2 lead to a broad spectrum of ...
    • Sin1 phosphorylation impairs mTORC2 complex integrity and inhibits downstream Akt signaling to suppress tumorigenesis 

      Liu, Pengda; Gan, Wenjian; Inuzuka, Hiroyuki; Lazorchak, Adam S; Gao, Daming; Arojo, Omotooke; Liu, Dou; Wan, Lixin; Zhai, Bo; Yu, Yonghao; Yuan, Min; Kim, Byeong Mo; Shaik, Shavali; Menon, Suchithra; Gygi, Steven P.; Lee, Tae Ho; Asara, John M; Manning, Brendan D.; Blenis, John; Su, Bing; Wei, Wenyi (2013)
      The mechanistic target of rapamycin (mTOR) functions as a critical regulator of cellular growth and metabolism by forming multi-component, yet functionally distinct complexes mTORC1 and mTORC2. Although mTORC2 has been ...
    • Splicing factor 1 modulates dietary restriction and TORC1 pathway longevity in C. elegans 

      Heintz, Caroline; Doktor, Thomas K.; Lanjuin, Anne E.; Escoubas, Caroline Camile Emiko; Zhang, Yue; Weir, Heather; Dutta, Sneha; Silva-García, Carlos Giovanni; Bruun, Gitte H.; Morantte, Ianessa; Hoxhaj, Gerta; Manning, Brendan D.; Andresen, Brage S.; Mair, William B (Springer Nature, 2016)
      Ageing is driven by a loss of transcriptional and protein homeostasis1, 2, 3 and is the key risk factor for multiple chronic diseases. Interventions that attenuate or reverse systemic dysfunction associated with age therefore ...
    • SREBP: A Key Effector of mTORC1 Signaling in Metabolism and Cancer 

      Yecies, Jessica (2013-01-02)
      The mammalian target of rapamycin complex 1 (mTORC1), a master regulator of cell growth and proliferation, is aberrantly activated in cancer, genetic tumor syndromes and obesity. Much progress has been made to understand ...
    • Therapeutic Trial of Metformin and Bortezomib in a Mouse Model of Tuberous Sclerosis Complex (TSC) 

      Auricchio, Neil; Malinowska, Izabela A; Shaw, Reuben; Manning, Brendan D.; Kwiatkowski, David Joseph (Public Library of Science, 2012)
      Tuberous sclerosis complex (TSC) is a human genetic disorder in which loss of either TSC1 or TSC2 leads to development of hamartoma lesions, which can progress and be life-threatening or fatal. The TSC1/TSC2 protein complex ...
    • The TSC-mTOR pathway regulates macrophage polarization 

      Byles, Vanessa; Covarrubias, Anthony J.; Ben-Sahra, Issam; Lamming, Dudley W.; Sabatini, David M.; Manning, Brendan D.; Horng, Tiffany (2013)
      Macrophages are able to polarize to proinflammatory M1 or alternative M2 states with distinct phenotypes and physiological functions. How metabolic status regulates macrophage polarization remains not well understood, and ...