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TSC1/2 Complex and Tuberous Sclerosis

TSC1/2 Complex and Tuberous Sclerosis . Devin Gibbs. Tuberous Sclerosis Causes Hamartomas. Mutations in TSC1/2 Cause Tuberous Sclerosis . TSC1/2 Mediates Cell Growth . TSC1/2 Mediates Cell Proliferation. TSC1/2 Integrates Growth and Energy Signals .

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TSC1/2 Complex and Tuberous Sclerosis

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  1. TSC1/2 Complex and Tuberous Sclerosis Devin Gibbs

  2. Tuberous Sclerosis Causes Hamartomas

  3. Mutations in TSC1/2 Cause Tuberous Sclerosis

  4. TSC1/2 Mediates Cell Growth

  5. TSC1/2 Mediates Cell Proliferation

  6. TSC1/2 Integrates Growth and Energy Signals

  7. A Diverse Array of Mutations can Cause Tuberous Sclerosis

  8. TSC1/2 Knockout Results in Cell Growth and Neuronal Disorganization

  9. TSC1/TSC2 Knockout Increases mTOR Activation

  10. mTOR Inhibitors Are Promising Therapies mTOR Rapamycin FKBP

  11. Summary • The TSC1/2 complex acts as a tumor suppressor to monitor growth and energy signals and inhibit cell cycle progression through inhibiting mTOR and β-catenin. • Loss of function mutations in TSC1 and/or TSC2 lead to constitutive activation of mTOR and upregulation of β-catenin. • mTOR inhibitors show promise in treating TSC.

  12. References • Ballou, L., & Lin, R. (2008). Rapamycin and mTOR kinase inhibitors. J Chem Biol., 1(1-4), 27-36. • Crino, P. B., Nathanson, K. L., & Henske, E. P. (2006). The tuberous sclerosis complex. N Engl J Med, 355(13), 1345-1356. doi: 10.1056/NEJMra055323 • Crino, P. B., Nathanson, K. L., & Henske, E. P. (2006). The tuberous sclerosis complex. N Engl J Med, 355(13), 1345-1356. doi: 10.1056/NEJMra055323 • Jones, A. C., Shyamsundar, M. M., Thomas, M. W., Maynard, J., Idziaszczyk, S., Tomkins, S., . . . Cheadle, J. P. (1999). Comprehensive mutation analysis of TSC1 and TSC2-and phenotypic correlations in 150 families with tuberous sclerosis. American Journal of Human Genetics, 64(5), 1305-1315. doi: 10.1086/302381 • Mak, B. C., Kenerson, H. L., Aicher, L. D., Barnes, E. A., & Yeung, R. S. (2005). Aberrant β-catenin signaling in tuberous sclerosis. The American Journal of Pathology, 167(1), 107-116. doi: 10.1016/S0002-9440(10)62958-6 • März, A. M., Fabian, A., Kozany, C., Bracher, A., & Hausch, F. (2013). Large FK506-binding proteins shape the pharmacology of rapamycin. Molecular and Cellular Biology, 33(7), 1357-1367. doi: 10.1128/MCB.00678-12 • Tomasoni, R., & Mondino, A. (2011). The tuberous sclerosis complex: Balancing proliferation and survival. Biochemical Society Transactions, 39(2), 466-471. doi: 10.1042/BST0390466; 10.1042/BST0390466 • Yao, J., Phan, A., Jehl, V., Shah, G., & Meric-Bernstam, F. (2013). Everolimus in advanced pancreatic neuroendocrine tumors: The clinical experience.  . Cancer Res., 73(5), 1449-53. • Zeng, L., Rensing, N. R., Zhang, B., Gutmann, D. H., Gambello, M. J., & Wong, M. (2011). Tsc2 gene inactivation causes a more severe epilepsy phenotype than Tsc1 inactivation in a mouse model of tuberous sclerosis complex. Human Molecular Genetics, 20(3), 445-454. doi: 10.1093/hmg/ddq491

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