This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ubiquitin-proteasome system (UPS) mediated proteolysis is the major protein turnover pathway in the cell. UPS dysfunction may play an important role in the pathogenesis of many human diseases, including highly lethal and disabling diseases such as Alzheimer's Huntington's disease, and a substantial subset of congestive heart failure. Therefore, studies on the regulation and function of the UPS have significant clinical implications. This project will determine if components of the 20S proteasome can be overexpressed individually at the protein level. The steady-state transcript levels as well as protein levels of a wild-type or missense mutant PSB5 transgene in the heart of cardiac-specific conditional transgenic (TG) mouse model will be measured during Northern and Western blot analyses, respectively. The expression of PSB5 will then be compared at both mRNA and protein levels. Differential changes in the expression between mRNA and protein levels and between TG and non-TG hearts would provide insights into the regulation of this critical component of the 20S proteasome. An alternative project would be to probe if the proteolytic function of the UPS is impaired in the brain of a mouse model of Huntington's diseases, using our newly created GFPdgn mouse model as readout.
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