Feedback control of prion formation and propagation by the ribosome-associated chaperone complex

被引:37
作者
Kiktev, Denis A. [1 ,2 ,3 ]
Melomed, Mikhail M. [1 ,2 ]
Lu, Caroline D. [1 ,2 ]
Newnam, Gary P. [1 ,2 ]
Chernoff, Yury O. [1 ,2 ,3 ]
机构
[1] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA
[2] Georgia Inst Technol, Inst Bioengn & Biosci, Atlanta, GA 30332 USA
[3] St Petersburg State Univ, Lab Amyloid Biol, St Petersburg 199034, Russia
关键词
DE-NOVO APPEARANCE; SACCHAROMYCES-CEREVISIAE; YEAST PRION; PSI+ PRION; TRANSLATION TERMINATION; PROTEIN; HSP70; HSP104; DETERMINANT; PSI(+);
D O I
10.1111/mmi.12960
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cross-beta fibrous protein aggregates (amyloids and amyloid-based prions) are found in mammals (including humans) and fungi (including yeast), and are associated with both diseases and heritable traits. The Hsp104/70/40 chaperone machinery controls propagation of yeast prions. The Hsp70 chaperones Ssa and Ssb show opposite effects on [PSI+], a prion form of the translation termination factor Sup35 (eRF3). Ssb is bound to translating ribosomes via ribosome-associated complex (RAC), composed of Hsp40-Zuo1 and Hsp70-Ssz1. Here we demonstrate that RAC disruption increases de novo prion formation in a manner similar to Ssb depletion, but interferes with prion propagation in a manner similar to Ssb overproduction. Release of Ssb into the cytosol in RAC-deficient cells antagonizes binding of Ssa to amyloids. Thus, propagation of an amyloid formed because of lack of ribosome-associated Ssb can be counteracted by cytosolic Ssb, generating a feedback regulatory circuit. Release of Ssb from ribosomes is also observed in wild-type cells during growth in poor synthetic medium. Ssb is, in a significant part, responsible for the prion destabilization in these conditions, underlining the physiological relevance of the Ssb-based regulatory circuit.
引用
收藏
页码:621 / 632
页数:12
相关论文
共 60 条
[1]   A Systematic Survey Identifies Prions and Illuminates Sequence Features of Prionogenic Proteins [J].
Alberti, Simon ;
Halfmann, Randal ;
King, Oliver ;
Kapila, Atul ;
Lindquist, Susan .
CELL, 2009, 137 (01) :146-158
[2]   Hsp70 chaperones as modulators of prion life cycle:: Novel effects of Ssa and Ssb on the Sacharomyces cerevisiae prion [PSI+] [J].
Allen, KD ;
Wegrzyn, RD ;
Chernova, TA ;
Müller, S ;
Newnam, GP ;
Winslett, PA ;
Wittich, KB ;
Wilkinson, KD ;
Chernoff, YO .
GENETICS, 2005, 169 (03) :1227-1242
[3]   Variant-specific [PSI+] infection is transmitted by Sup35 polymers within [PSI+] aggregates with heterogeneous protein composition [J].
Bagriantsev, Sviatoslav N. ;
Gracheva, Elena O. ;
Richmond, Janet E. ;
Liebman, Susan W. .
MOLECULAR BIOLOGY OF THE CELL, 2008, 19 (06) :2433-2443
[4]   Analysis of amyloid aggregates using agarose gel electrophoresis [J].
Bagriantsev, Sviatoslav N. ;
Kushnirov, Vitaly V. ;
Liebman, Susan W. .
AMYLOID, PRIONS, AND OTHER PROTEIN AGGREGATES, PT B, 2006, 412 :33-48
[5]   Prion variant maintained only at high levels of the Hsp104 disaggregase [J].
Borchsenius, AS ;
Müller, S ;
Newnam, GP ;
Inge-Vechtomov, SG ;
Chernoff, YO .
CURRENT GENETICS, 2006, 49 (01) :21-29
[6]   Ssb1 chaperone is a [PSI+] prion-curing factor [J].
Chacinska, A ;
Szczesniak, B ;
Kochneva-Pervukhova, NV ;
Kushnirov, VV ;
Ter-Avanesyan, MD ;
Boguta, M .
CURRENT GENETICS, 2001, 39 (02) :62-67
[7]   Evolutionary conservation of prion-forming abilities of the yeast Sup35 protein [J].
Chernoff, YO ;
Galkin, AP ;
Lewitin, E ;
Chernova, TA ;
Newnam, GP ;
Belenkiy, SM .
MOLECULAR MICROBIOLOGY, 2000, 35 (04) :865-876
[8]  
Chernoff YO, 1999, MOL CELL BIOL, V19, P8103
[9]  
Chernoff YO, 2002, METHOD ENZYMOL, V351, P499
[10]   ROLE OF THE CHAPERONE PROTEIN HSP104 IN PROPAGATION OF THE YEAST PRION-LIKE FACTOR [PSI(+)] [J].
CHERNOFF, YO ;
LINDQUIST, SL ;
ONO, B ;
INGEVECHTOMOV, SG ;
LIEBMAN, SW .
SCIENCE, 1995, 268 (5212) :880-884