Associate Professor, Molecular Pharmacology and Biological Chemistry; Feinberg School of Medicine
Cancer Cell Biology
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Prion proteins are capable of existing in multiple stable conformations, at least one of which is infectious. It is generally accepted that prion (PrPSc) is the responsible agent for the devastating neurodegenerative disorders known as transmissible spongiform encephalopathies or prion diseases. Interestingly, in the budding yeast, Saccharomyces cerevisiae, there are several epigenetic elements that are also transmitted as heritable protein conformations, known as yeast prions. Our laboratory uses yeast a model organism to understand how a prion protein acquires its infectious prion conformations and how such conformations are maintained in vivo. Our ultimate goal is to dissect the initiation and propagation processes of prionogenesis, and to identify important cellular factors required in each of these processes.
We have recently identified a new yeast prion protein, Swi1, a subunit of the evolutionarily conserved chromatin remodeling complex, SWI/SNF. Swi1 is able to switch conformation to become a prion which is termed as [SWI+]. Swi1 is aggregated in [SWI+] cells but soluble in non-prion cells. Yeast cells bearing the Swi1 prion show partial loss-of-function phenotype of SWI/SNF. Interestingly, the loss and gain of Swi1 prion can be experimentally manipulated in a laboratory setting. Since mammalian SWI/SNF has tumor suppression function and mutations in several subunits of human SWI/SNF are linked to tumorigenesis, our [SWI+] study might uncover a potential link between prions and cancer biology.