Open Access. Powered by Scholars. Published by Universities.®

Medicine and Health Sciences Commons

Open Access. Powered by Scholars. Published by Universities.®

Medical Sciences

University of Alabama at Birmingham

Theses/Dissertations

2010

Proteasome

Articles 1 - 4 of 4

Full-Text Articles in Medicine and Health Sciences

The Role Of Usp14 In Regulating Synaptic Development And Function Of The Neuromuscular Junctions, Ping-Chung Chen Jan 2010

The Role Of Usp14 In Regulating Synaptic Development And Function Of The Neuromuscular Junctions, Ping-Chung Chen

All ETDs from UAB

The ubiquitin proteasome system (UPS) plays critical roles in regulating multiple cellular functions, including protein abundance, trafficking, and cell signaling. In the nervous system, the UPS has been implicated in controlling a wide diversity of cellular process such as synaptic transmission, axon outgrowth, axon targeting, and synapse development. Although impairment of the UPS is observed in both neurodegenerative and developmental diseases, the mechanisms underlying how UPS dysregulation contributes to disease pathogenesis are not known. The proteasome, an approximate 2.5 megadaltons protein complex composed of 19S and 20S assemblies, is the site of ubiquitin-dependent protein degradation. Recent studies have demonstrated dysfunction …


Regulation Of Apoptosis By Smac, Iaps , And The Ubiquitin Proteasome System, Stephen Peter Burke Jan 2010

Regulation Of Apoptosis By Smac, Iaps , And The Ubiquitin Proteasome System, Stephen Peter Burke

All ETDs from UAB

Apoptosis, or programmed cell death, is essential for the development and maintenance of mammalian tissues. Activation of cysteinyl aspartate specific proteases, called caspases, is crucial to the implementation apoptosis. During apoptosis, the second mito-chondrial derived activator of caspase (Smac), augments caspase activity by antagonizing the inhibitor of apoptosis proteins (IAPs) down-regulation of caspase function. Smac protein synthesis occurs in the cytosol from a nuclear gene. Mitochondrial import of Smac leads to proteolytic removal of the first 55 amino acids, exposing a novel amino-terminus composed Ala56-Val-Pro-Ile59, which is an inhibitor of apoptosis binding motif (IBM). The IBM facilitates the interactions with …


The Role Of Post-Translational Modifications And Valosin-Containing Protein In The Turnover And Stability Of The Microtubule-Associated Protein Tau, Philip James Dolan Jan 2010

The Role Of Post-Translational Modifications And Valosin-Containing Protein In The Turnover And Stability Of The Microtubule-Associated Protein Tau, Philip James Dolan

All ETDs from UAB

Alzheimer Disease (AD) is pathologically characterized by the appearance of senile plaques composed of ß-amyloid and neurofibrillary tangles composed of the microtubule-associated protein tau. During the development of AD pathology, tau is hyperphosphorylated and aberrantly cleaved, both of which potentially contribute to its pathogenic and fibrillogenic nature. The accumulative nature of these post-translational products, and their contribution to tau pathology, has led to a great deal of study regarding mechanisms for both the maintenance of tau stability and degradation. The first part of this study reviews the developments regarding the contribution of phosphorylated tau to different physiological and pathological processes. …


Usp14: A Link Between The Proteasome And Synaptic Function, Brandon John Walters Jan 2010

Usp14: A Link Between The Proteasome And Synaptic Function, Brandon John Walters

All ETDs from UAB

The ubiquitin proteasome system (UPS) is a coordinated process by which the cell can control protein distribution and abundance. Proteins are marked for turnover by the construction of a polyubiquitin chain on the protein substrate. Once engaged by the proteasome, the ubiquitin side-chain is disassembled by proteasomal deubiquitinating enzymes (DUBs), preventing entry of ubiquitin into the proteasome and recycling it for use in future reactions. One of the DUBs that resides on the proteasome is Ubiquitin Specific Protease 14 (Usp14), which is mutated in the ataxia (axJ) mice. This mutation results in pronounced physical deficits and, unexpectedly, a deficit in …