HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Prion Degradation Discovery

Prions are infectious proteins that can self-propagate without nucleic acids. Mammalian prions cause fatal neurodegenerative diseases such as sheep scrapie, "mad cow" disease, and Creutzfeldt-Jacob disease, whereas in yeast they are non-chromosomal genes such as [URE3], [PSI⁺] and [PIN⁺]. In cells, degradation of abnormal or damaged proteins occurs in part via the ubiquitinproteasome system (UPS), in which proteins are targeted for destruction by the attachment of ubiquitin tags. Mutations in different UPS components have been found to be associated with disorders linked to amyloid-like protein aggregation, such as Alzheimer and Parkinson diseases.

Deletion of UBC4 or UBP6 decreases [PSI+] curing by excess Hsp104.

In this Paper of the Week, Kim D. Allen and colleagues use the yeast prion [PSI⁺] to analyze the possible involvement of the UPS in modulation of prion formation, propagation, and clearance. Previously, they found that overproduction of the chaperone protein Hsp104 results in loss of [PSI⁺]. Here they show that this effect is decreased by deletion of either the gene coding for one of the major yeast ubiquitin-conjugating enzymes, Ubc4, or the gene coding for the ubiquitin-recycling enzyme, Ubp6. Moreover, deletion of Ubc4 significantly increases spontaneous formation of [PSI⁺]. These results imply that the UPS is one of the major modulators of prion formation and clearance in the yeast cells.

FOOTNOTES

See referenced article, J. Biol. Chem. 2007, 282, 3004-3013

[More Papers of the Week]