Evidence that S6K1, but not 4E-BP1, mediates skeletal muscle pathology associated with loss of A-type lamins.

ABSTRACT: The mechanistic target of rapamycin (mTOR) signaling pathway plays a central role in aging and a number of different disease states. Rapamycin, which suppresses activity of the mTOR complex 1 (mTORC1), shows preclinical (and sometimes clinical) efficacy in a number of disease models. Among these are Lmna^-/- mice, which serve as a mouse model for dystrophy-associated laminopathies. To confirm that elevated mTORC1 signaling is responsible for the pathology manifested in Lmna^-/- mice and to decipher downstream genetic mechanisms underlying the benefits of rapamycin, we tested in Lmna^-/- mice whether survival could be extended and disease pathology suppressed either by reduced levels of S6K1 or enhanced levels of 4E-BP1

SUBMITTER: Liao CY 

PROVIDER: S-EPMC5931234 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature