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PMID: 10823922 Published · ppublish English Journal Article

A protein required for prion generation: [URE3] induction requires the Ras-regulated Mks1 protein.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 12 ·2000-06-06 ·Pages 6625-9

Edskes HK, Wickner RB

Abstract

Infectious proteins (prions) can arise de novo as well as by transmission from another individual. De novo prion generation is believed responsible for most cases of Creutzfeldt-Jakob disease and for initiating the mad cow disease epidemic. However, the cellular components needed for prion generation have not been identified in any system. The [URE3] prion of Saccharomyces cerevisiae is an infectious form of Ure2p, apparently a self-propagating amyloid. We now demonstrate a protein required for de novo prion generation. Mks1p negatively regulates Ure2p and is itself negatively regulated by the presence of ammonia and by the Ras-cAMP pathway. We find that in mks1Delta strains, de novo generation of the [URE3] prion is blocked, although [URE3] introduced from another strain is expressed and propagates stably. Ras2(Val19) increases cAMP production and also blocks [URE3] generation. These results emphasize the distinction between prion generation and propagation, and they show that cellular regulatory mechanisms can critically affect prion generation.

MeSH Terms
Cyclic AMP/physiology Fungal Proteins/physiology Prions/biosynthesis Repressor Proteins Saccharomyces cerevisiae/physiology Saccharomyces cerevisiae Proteins Transcription Factors ras Proteins/physiology
Chemicals
Fungal Proteins MKS1 protein, S cerevisiae Prions Repressor Proteins Saccharomyces cerevisiae Proteins Transcription Factors Cyclic AMP ras Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Edskes H K
Laboratory of Biochemistry and Genetics, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Building 8, Room 225, 8 Center Drive, MSC 0830, Bethesda, MD 20892-0830, USA.
Wickner R B
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.120168697
Published
2000-06-06
Pages
6625-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC18680
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.120168697 PMC Full Text View journal details
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