Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 1 of 1
Full-Text Articles in Life Sciences
Molecular Mechanisms Underlying The Suppression Of Cardiomyocyte Necroptosis By The Cop9 Signalosome In Mice, Megan T. Lewno
Molecular Mechanisms Underlying The Suppression Of Cardiomyocyte Necroptosis By The Cop9 Signalosome In Mice, Megan T. Lewno
Dissertations and Theses
Background: Within a large subset of heart failure, cardiac ubiquitin-proteasome system (UPS) inadequacy is causative. A vital UPS regulator is the COP9 signalosome (CSN). The CSN holocomplex is formed by 8 unique protein subunits (COPS1~COPS8) and regulates Cullin-RING ligases via Cullin deneddylation. Cardiomyocyte-restricted knockout (cko) of Cops8 causes massive cardiomyocyte necroptosis via the RIPK1-RIPK3-MLKL pathway, resulting in dilated cardiomyopathy (DCM) and shortened lifespan in mice. CSN’s deneddylase resides in COPS5 and Cops5-cko has not been explored. It is important to investigate how the necroptotic pathway within cardiomyocytes is activated in Cops8-cko mice as cardiomyocyte necroptosis has been shown to play …