The Saccharomyces cerevisiae heat shock protein Hsp31 is a stress-inducible homodimeric protein that is involved in diauxicshift reprogramming and has glyoxalase activity. We show thatsubstoichiometric concentrations of Hsp31 can abrogate aggrega-tion of a broad array of substrates in vitro. Hsp31 also modulates the aggregation of -synuclein ( Syn), a target of the chaperoneactivity of human DJ-1, an Hsp31 homolog. We demonstrate thatHsp31 is able to suppress the in vitro fibrillization or aggregation of Syn, citrate synthase and insulin. Chaperone activity was also observed in vivo because constitutive overexpression of Hsp31 reduced the incidence of Syn cytoplasmic foci, and yeast cells were rescued from Syn-generated proteotoxicity upon Hsp31overexpression. Moreover, we showed that Hsp31 protein levels are increased byH2O2, in the diauxic phase of normal growth con-ditions, and in cells under Syn-mediated proteotoxic stress. Weshow that Hsp31 chaperone activity and not the methylglyoxalaseactivity or the autophagy pathway drives the protective effects.Wealso demonstrate reduced aggregation of the Sup35 prion domain,PrD-Sup35, as visualized by fluorescent protein fusions. In addi-tion, Hsp31 acts on its substrates prior to the formation of largeaggregates because Hsp31 does not mutually localize with prionaggregates, and it prevents the formation of detectable in vitro Syn fibrils. These studies establish that the protective role ofHsp31 against cellular stress is achieved by chaperone activity thatintervenes early in the protein misfolding process and is effectiveona wide spectrum of substrate proteins, including Synandprion proteins.


This is the published version of Tsai CJ, Aslam K, Drendel HM, Asiago JM, Goode KM, Paul LN, Rochet JC, Hazbun TR. Hsp31 Is a Stress Response Chaperone That Intervenes in the Protein Misfolding Process. J Biol Chem. 2015 Oct 9;290(41):24816-34. doi: 10.1074/jbc.M115.678367. Epub 2015 Aug 25. PMID: 26306045; PMCID: PMC4598993.


Parkinson disease, alpha-synuclein, enzyme, molecular chaperone, multifunctional protein, prion, protein misfolding, small heat shock protein (sHsp), stress response, yeast

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