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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 …
Mechanisms Of Substrate Recognition By The Cul3-Based E3 Ligase, Katia Graziella De Oliveira Rebola
Mechanisms Of Substrate Recognition By The Cul3-Based E3 Ligase, Katia Graziella De Oliveira Rebola
Dissertations and Theses
Cul3-based E3 ligase is responsible for regulating a variety of cellular pathways, many of which are known to have profound effects on the proper function of multicellular organisms. Although progress over the past years has been truly impressive, our understanding of the mechanisms of E2 recruitment and selection by the BCR complex and all the roles that Cul3 plays on kidneys remains in its infancy. To explore these aspects, this dissertation aims to analyze the Cul3 complex using two different approaches: (1) We used the powerful tool of chimeric analysis to map the essential domain binding characteristics of Cul3 taking …