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We are using
biochemical, cell biological, genetic, and molecular
approaches in conjunction with the yeast system to better
understand the function of several proteases that act on
isoprenylated proteins. Examples of isoprenylated
proteins include the Ras family of oncoproteins,
Ras-related proteins, kinases, and secreted fungal mating
pheromones, among many others. Understanding the function
of these proteases may lead to novel therapeutic
strategies for cancer, Alzheimer's disease, and other
diseases. • Rce1p is an ER membrane-localized protease of unknown mechanism. This protease is essential for the maturation of isoprenylated molecules that are involved in cellular transformation (e.g., Ras and RhoB). We aim to define the proteolytic mechanism of Rce1p and to develop pharmacological inhibitors that have anti-tumor potential. Rce1p has partial overlapping function with the ER membrane-localized, zinc-dependent Ste24p protease, which has been linked to premature aging (progeria) because of its role in the processing of lamin A. Thus, we are also trying to understand the functional differences of Rce1p and Ste24p to better understand their relative physiological importance. • Ste23p and Axl1p are zinc-dependent metalloproteases that are required for the maturation of the isoprenylated yeast a-factor mating pheromone. These proteases are part of the M16 family of metalloproteases, which includes the insulin-degrading enzyme that has a proposed protective function in Alzheimer's disease (AD). Our research on Ste23p and Axl1p is designed is to gain a better understanding of these largely uncharacterized yeast proteases and the M16 metalloprotease family as a whole, thus potentially providing novel insight into new methods for the treatment of AD.
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Course Related Information
FRES1020 resources - The Contributions of Underrepresented Minorities to Today's Understanding of Biology.
BCMB8005 resources - BCMB Graduate Professional Development.
BCMB8020 resources - Graduate Biochemistry and Molecular Biology II.
BCMB8120 resources - Advanced Topics in Gene Expression.
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