Accession Number:

AD1053974

Title:

Defining Translational Reprogramming in Tuberous Sclerosis Complex

Descriptive Note:

Technical Report,01 Jul 2014,30 Jun 2017

Corporate Author:

Cornell University Ithaca United States

Personal Author(s):

Report Date:

2017-09-01

Pagination or Media Count:

41.0

Abstract:

Inactivating mutations in the TSC1 and TSC2 tumor suppressor genes lead to the disease tuberous sclerosis complex TSC. The TSC1TSC2complex 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 Consistent with this hypothesis, in unpublished data, we have found prevailing alternative translation that re-shapes proteome landscape.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.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE