Vacuolar Proteases of Saccharomyces cerevisiae: Characterization of an Overlooked Homolog Leads to New Functional Insights
dc.contributor.author | Parzych, Katherine | |
dc.date.accessioned | 2018-01-31T18:23:08Z | |
dc.date.available | 2018-01-31T18:23:08Z | |
dc.date.issued | 2017 | |
dc.date.submitted | ||
dc.identifier.uri | https://hdl.handle.net/2027.42/140972 | |
dc.description.abstract | Hydrolysis within the vacuole in yeast and lysosome in mammals is required for the degradation and recycling of a vast array of substrates. In humans, defects in lysosomal hydrolysis and efflux contribute to a class of diseases referred to as lysosomal storage disorders that affect 1/8000 live births. Despite the importance of these processes, many of the proteins and regulatory mechanisms involved in hydrolysis and efflux are poorly understood, especially those involved in proteolysis. Using the yeast Saccharomyces cerevisiae as a model, I employed a combination of molecular and cellular biological techniques to characterize a previously overlooked homolog of the protease Prc1 (carboxypeptidase Y), Ybr139w. I demonstrated that these two homologous serine carboxypeptidases are required for proper functioning of the vacuole; cells lacking Prc1 and Ybr139w exhibit defects in zymogen activation, amino acid recycling, and degradation of autophagic bodies delivered to the vacuole via macroautophagy (hereafter autophagy). Based on its function in the terminal steps of autophagy, I have proposed that Ybr139w be renamed as Atg42. This work expands our understanding of vacuolar proteases and encourages improved characterization of these proteins together with potential homologs. Such an undertaking will enable further dissection of the mechanisms of proteolytic activation of zymogens and the terminal steps of autophagy, including lysis of the autophagic body, degradation of the cargo, and efflux of the resultant macromolecules. | |
dc.language.iso | en_US | |
dc.subject | Autophagy | |
dc.subject | Vacuole | |
dc.subject | Molecular biology | |
dc.subject | Yeast | |
dc.subject | Saccharomyces cerevisiae | |
dc.subject | Hydrolases | |
dc.title | Vacuolar Proteases of Saccharomyces cerevisiae: Characterization of an Overlooked Homolog Leads to New Functional Insights | |
dc.type | Thesis | en_US |
dc.description.thesisdegreename | PhD | en_US |
dc.description.thesisdegreediscipline | Molecular, Cellular, and Developmental Biology | |
dc.description.thesisdegreegrantor | University of Michigan, Horace H. Rackham School of Graduate Studies | |
dc.contributor.committeemember | Klionsky, Daniel J | |
dc.contributor.committeemember | Weisman, Lois S | |
dc.contributor.committeemember | Chapman, Matt R | |
dc.contributor.committeemember | Kumar, Anuj | |
dc.subject.hlbsecondlevel | Biological Chemistry | |
dc.subject.hlbsecondlevel | Genetics | |
dc.subject.hlbsecondlevel | Molecular, Cellular and Developmental Biology | |
dc.subject.hlbsecondlevel | Science (General) | |
dc.subject.hlbtoplevel | Health Sciences | |
dc.subject.hlbtoplevel | Science | |
dc.description.bitstreamurl | https://deepblue.lib.umich.edu/bitstream/2027.42/140972/1/parzykat_1.pdf | |
dc.identifier.orcid | 0000-0002-6263-0396 | |
dc.identifier.name-orcid | Parzych, Katherine; 0000-0002-6263-0396 | en_US |
dc.owningcollname | Dissertations and Theses (Ph.D. and Master's) |
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