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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 . - PowerPoint PPT Presentation
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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
A Diverse Array of Mutations can Cause Tuberous Sclerosis
TSC1/2 Knockout Results in Cell Growth and Neuronal Disorganization
TSC1/TSC2 Knockout Increases mTOR Activation
mTOR Inhibitors Are Promising Therapies
mTOR
FKBP
Rapamycin
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.
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• 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