Defining Translational Reprogramming in Tuberous Sclerosis Complex
Abstract
Inactivating mutations in the TSC1 and TSC2 tumor suppressor genes lead to the disease tuberous sclerosis complex (TSC). The TSC1/TSC2complex integrates multiple cues to regulate protein translation and cell growth via mammalian target of rapamycin complex 1 (mTORC1). Loss of TSC functions leads to constitutive activation of mTORC1 and uncontrolled mRNA translation. In recently published data, we discovered thatTSC2-deficient cells have increased protein synthesis but with reduced protein quality, leading us to hypothesize that disrupted protein homeostasis contributes to TSC pathophysiology. Consistent with this hypothesis, in unpublished data, we have found prevailing alternative translation that re-shapes proteome landscape. Our results suggest that translational re-programming can be targeted for therapeutic strategies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2017
- Accession Number
- AD1053974
Entities
People
- Shu-Bing Qian
Organizations
- Cornell University