NR AFFF
AU Hatin,I.; Bidou,L.; Cullin,C.; Rousset,J.P.
TI Translational errors as an early event in prion conversion
QU Cellular and Molecular Biology (Noisy-le-Grand, France) 2001; 47 Online Pub: OL23-8
PT journal article
AB A prion is an infectious, altered form of a cellular protein which can self-propagate and affect normal phenotype. Prion conversion has been observed for mammalian and yeast proteins but molecular mechanisms that trigger this process remain unclear. Up to now, only post-translational models have been explored. In this work, we tested the hypothesis that co-translational events may be implicated in the conformation changes of the Ure2p protein of Saccharomyces cerevisiae. This protein can adopt a prion conformation leading to an [URE3] phenotype which can be easily assessed and quantified. We analyzed the effect of two antibiotics, known to affect translation, on [URE3] conversion frequency. For cells treated with G418 we observed a parallel increase of translational errors rate and frequency of [URE3] conversion. By contrast, cycloheximide which was not found to affect translational fidelity, has no influence on the induction of [URE3] phenotype. These results raise the possibility that the mechanism of prion conversion might not only involve alternative structures of strictly identical molecules but also aberrant proteins resulting from translational errors.
MH Animal; Antibiotics, Aminoglycoside/pharmacology; Frameshifting, Ribosomal/drug effects; Gentamicins/pharmacology; Human; Phenotype; Prions/chemistry/*genetics; Protein Conformation; Protein Folding; Saccharomyces cerevisiae/chemistry/drug effects/*genetics; Saccharomyces cerevisiae Proteins/chemistry/*genetics; Support, Non-U.S. Gov't; *Translation, Genetic/drug effects
AD Institut de Genetique et Microbiologie, UMR CNRS C8621, Universite Paris-Sud, Orsay, France.
SP englisch
PO Frankreich