Accession Number : AD1018872

Title :   Defining Translational Reprogramming in Tuberous Sclerosis Complex

Descriptive Note : Technical Report,01 Jul 2015,30 Jun 2016

Corporate Author : Cornell University Ithaca United States

Personal Author(s) : Qian,Shu-Bing

Full Text :

Report Date : 01 Jul 2016

Pagination or Media Count : 33

Abstract : Inactivating mutations in the TSC1 and TSC2 tumor suppressor genes lead to the disease tuberous sclerosis complex (TSC). The TSC1/TSC2 complex integrates multiple cues to regulate proteintranslation and cell growth via mammalian target of rapamycin complex 1 (mTORC1). Loss of TSC functionsleads to constitutive activation of mTORC1 and uncontrolled mRNA translation. In recently published data, wediscovered that TSC2-deficient cells have increased protein synthesis but with reduced protein quality, leadingus to hypothesize that disrupted protein homeostasis contributes to TSC pathophysiology. Consistent with thishypothesis, in unpublished data, we have found prevailing alternative translation that re-shapes proteomelandscape. Our results suggest that translational re-programming can be targeted for therapeutic strategies

Descriptors :   genetic diseases , gene expression , organelles , rna stability , proteins , stem cells , amino acids , neoplasms , tissues (biology) , ribosomes , Transcription (Genetics) , stress (physiology) , response (biology)

Distribution Statement : APPROVED FOR PUBLIC RELEASE