A protein required for prion generation: [URE3] induction requires the Ras-regulated Mks1 protein.
نویسندگان
چکیده
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.
منابع مشابه
Revised 11/27/01 RTG-dependent mitochondria-to-nucleus signaling is regulated by MKS1 and is linked to the formation of the yeast prion [URE3]
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ورودعنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 97 12 شماره
صفحات -
تاریخ انتشار 2000