NDLI: De Novo Appearance and “Strain” Formation of Yeast Prion [PSI +] Are Regulated by the Heat-Shock Transcription Factor

Content Provider	PubMed Central
Author	Park, Kyung-won Hahn, Ji-sook Fan, Qing Thiele, Dennis J. Li, Liming
Copyright Year	2006
Abstract	Yeast prions are non-Mendelian genetic elements that are conferred by altered and self-propagating protein conformations. Such a protein conformation-based transmission is similar to that of PrPSc, the infectious protein responsible for prion diseases. Despite recent progress in understanding the molecular nature and epigenetic transmission of prions, the underlying mechanisms governing prion conformational switch and determining prion “strains” are not understood. We report here that the evolutionarily conserved heat-shock transcription factor (HSF) strongly influences yeast prion formation and strain determination. An hsf1 mutant lacking the amino-terminal activation domain inhibits the yeast prion [PSI +] formation whereas a mutant lacking the carboxyl-terminal activation domain promotes [PSI +] formation. Moreover, specific [PSI +] strains are preferentially formed in these mutants, demonstrating the importance of genetic makeup in determining de novo appearance of prion strains. Although these hsf1 mutants preferentially support the formation of certain [PSI +] strains, they are capable of receiving and faithfully propagating nonpreferable strains, suggesting that prion initiation and propagation are distinct processes requiring different cellular components. Our findings establish the importance of HSF in prion initiation and strain determination and imply a similar regulatory role of mammalian HSFs in the complex etiology of prion disease.
Related Links	http://dx.doi.org/10.1534/genetics.105.054221
Ending Page	47
Page Count	13
Starting Page	35
File Format	PDF
ISSN	00166731
Journal	Genetics
Issue Number	1
Volume Number	173
Language	English
Publisher	Copyright © 2006 by the Genetics Society of America
Publisher Date	2006-03-01
Access Restriction	Open
Rights Holder	Copyright © 2006 by the Genetics Society of America
Subject Keyword	Genetics Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics

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