hsp40一型在3种酵母阮病毒繁殖中的特异性.pdfVIP

Specificity of the J-protein Sis1 in the propagation of 3 yeast prions † ‡ Takashi Higurashi*, Justin K. Hines*, Chandan Sahi, Rebecca Aron , and Elizabeth A. Craig Department of Biochemistry, University of Wisconsin, 445 Biochemistry Addition, 433 Babcock Drive, Madison, WI 53706 Contributed by Elizabeth A. Craig, September 9, 2008 (sent for review August 13, 2008) Yeast prions, such as [PSI], [RNQ], and [URE3], are heritable propagation implies an involvement of an unidentified J-protein elements formed by proteins capable of acquiring self-perpetuat- as well. ing conformations. Their propagation is dependent on fragmen- The currently favored model for prion propagation posits tation of the amyloid protein complexes formed to generate the chaperone-mediated fragmentation of prion complexes to pro- additional seeds necessary for conversion of nascent soluble pro- duce sufficient prion seeds to assure consistent transmission of tein to the prion conformation. We report that, in addition to its seeds to daughter cells, thus maintaining the prion in the cell known role in [RNQ] propagation, Sis1, a J-protein cochaperone population (2, 10–14). Supporting this model, inhibition of of Hsp70 Ssa, is also specifically required for propagation of [PSI] Hsp104 activity results in an increase in the size of Sup35 and and [URE3]. Whereas both [RNQ] and [URE3] are cured rapidly Rnq1 prion complexes and subsequent prion loss, which has been upon SIS1 repression, [PSI] loss is markedly slower. This disparity shown in the case of [PSI ] to be dependent on cell division (10, cannot be explained simply by differences in seed number, as 11