Protein disaggregation mediated by heat-shock protein Hspl04

Parsell, Dawn A.; Kowal, Anthony S.; Singer, Mike A.; Lindquist, Susan

doi:10.1038/372475a0

Cited by 846 publications

(743 citation statements)

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“…The phenomenon of disaggregation was first reported in S. cerevisiae where heat denatured proteins can be efficiently reactivated by the cooperative action of Hsp70-Hsp40 and the oligomeric, ring forming AAA+ ATPase chaperone Hsp104 (Glover and Lindquist, 1998;Parsell et al, 1994). Soon after the discovery of Hsp104 disaggregase in yeast, an orthologous protein called ClpB was shown to possess disaggregation activity in E. coli and in chloroplasts and mitochondria of higher eukaryotes .…”

Section: Ii441 Chaperone Mediated Refolding and Disaggregationmentioning

confidence: 99%

Firefly luciferase mutants as sensors of proteome stress

et al. 2011

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Section: Ii441 Chaperone Mediated Refolding and Disaggregationmentioning

confidence: 99%

Firefly luciferase mutants as sensors of proteome stress

et al. 2011

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“…For example, yeast cells expressing Hsp104p are 1000 times more viable after exposure to temperatures Ն50°C or to an ethanol concentration of 20% than cells carrying deletions of HSP104 (Sanchez and Lindquist, 1990;Sanchez et al, 1992). This survival capacity is directly attributable to Hsp104p's ability to resolubilize protein aggregates and, together with Hsp70p and Hsp40p, return them to their folded and active states (Parsell et al, 1994;Glover and Lindquist, 1998;Goloubinoff et al, 1999). This is in contrast to other heat shock proteins, which generally act by preventing aggregate accumulation or by promoting the degradation of misfolded proteins (Schirmer et al, 1996;Zolkiewski, 1999).…”

Section: Introductionmentioning

confidence: 95%

Section: Thermotolerance and Atpase Assaysmentioning

confidence: 99%

“…The same strain and plasmids used for the light/fluorescence microscopy were similarly induced before fixation for electron microscopy. The electron microscopy was carried out as described previously (Parsell et al, 1994).Wild-type (A3224) and suppressor (A3685, A3686) strains carrying the GFP-CDC3 and HSP104(G217S/T499I)-b/Leu plasmids were analyzed live after a 12-h induction by using the Lab-Tek II chambered #1.5 German coverglass system (Nalge Nunc International, Naperville, IL). Images were obtained using an Axiovert S100TV microscope (Carl Zeiss) interfaced to a Bio-Rad MRC1024 confocal system.…”

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Dominant Gain-of-Function Mutations in Hsp104p Reveal Crucial Roles for the Middle Region

Schirmer

Homann

Kowal

et al. 2004

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Heat-shock protein 104 (Hsp104p) is a protein-remodeling factor that promotes survival after extreme stress by disassembling aggregated proteins and can either promote or prevent the propagation of prions (protein-based genetic elements). Hsp104p can be greatly overexpressed without slowing growth, suggesting tight control of its powerful protein-remodeling activities. We isolated point mutations in Hsp104p that interfere with this control and block cell growth. Each mutant contained alterations in the middle region (MR). Each of the three MR point mutations analyzed in detail had distinct phenotypes. In combination with nucleotide binding site mutations, Hsp104p T499I altered bud morphology and caused septin mislocalization, colocalizing with the misplaced septins. Point mutations in the septin Cdc12p suppressed this phenotype, suggesting that it is due to direct Hsp104p-septin interactions. Hsp104p A503V did not perturb morphology but stopped cell growth. Remarkably, when expressed transiently, the mutant protein promoted survival after extreme stress as effectively as did wild-type Hsp104p. Hsp104p A509D had no deleterious effects on growth or morphology but had a greatly reduced ability to promote thermotolerance. That mutations in an 11-amino acid stretch of the MR have such profound and diverse effects suggests the MR plays a central role in regulating Hsp104p function. INTRODUCTIONThe AAA ϩ proteins are ATPases associated with various cellular activities. They are important proteins with a great diversity of functions, including protein folding, membrane trafficking, organelle biogenesis, proteolysis, intracellular motility, and DNA replication (Neuwald et al., 1999;Vale, 2000;Ogura and Wilkinson, 2001). Little is known about how most AAA ϩ proteins recognize substrates and use ATP binding and hydrolysis to remodel them. The intrinsic complexity and multiplicity of conformational states of the AAA ϩ proteins make them difficult to study. The Clp/ HSP100 proteins are members of the AAA ϩ superfamily and have been the subject of intense biochemical analysis in vitro and genetic analysis in vivo (Wickner et al., 1999;Glover and Tkach, 2001). The functional unit of the yeast HSP100 heatshock protein 104 (Hsp104p) is composed of six monomers, each with two ATP binding sites (nucleotide binding domains one and two; NBD1 and NBD2) flanked by aminoterminal, middle, and carboxy-terminal regions (Figure 1).Hsp104p has remarkable functions, one of which is to allow survival after extreme stress. For example, yeast cells expressing Hsp104p are 1000 times more viable after exposure to temperatures Ն50°C or to an ethanol concentration of 20% than cells carrying deletions of HSP104 (Sanchez and Lindquist, 1990;Sanchez et al., 1992). This survival capacity is directly attributable to Hsp104p's ability to resolubilize protein aggregates and, together with Hsp70p and Hsp40p, return them to their folded and active states (Parsell et al., 1994;Glover and Lindquist, 1998;Goloubinoff et al., 1999). This is in contrast to other...

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“…For example, hsc70 has been shown to interact with nascent proteins, and is believed to playa role in proper folding of the nascent proteins [3]. Recently, it has been shown that the yeast high molecular weight heat shock protein hsplO4 resolubilizes heat-inactivated insoluble aggregates of proteins [4]. The heat shock proteins are also involved in protein degradation.…”

Section: Introductionmentioning

confidence: 99%

HPV 16 E7 oncoprotein induces expression of a 110 kDa heat shock protein

1995

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Heat shock protein genes are induced by various kinds of stress. Besides stress, the heat shock family gene hsp70 has been shown to be induced by growth-stimulating agents such as the DNA virus oncoproteins and serum. Here, we report cloning of a novel cDNA that encodes a 100 kDa heat shock proteinrelated polypeptide as a human papillomavirus oncoprotein E7-inducible gene. E7 induces expression of this heat shock protein at the level of RNA synthesis. Moreover, the induction of this heat shock protein-mRNA was dependent on the conserved region 2 of the E7 protein, which is essential for binding to the proteins of the retinoblastoma family.

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Protein disaggregation mediated by heat-shock protein Hspl04

Cited by 846 publications

References 21 publications

Firefly luciferase mutants as sensors of proteome stress

Firefly luciferase mutants as sensors of proteome stress

Dominant Gain-of-Function Mutations in Hsp104p Reveal Crucial Roles for the Middle Region

HPV 16 E7 oncoprotein induces expression of a 110 kDa heat shock protein

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