A critical role for the proteasome activator PA28 in the Hsp90-dependent protein refolding - PubMed (original) (raw)

. 2000 Mar 24;275(12):9055-61.

doi: 10.1074/jbc.275.12.9055.

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A critical role for the proteasome activator PA28 in the Hsp90-dependent protein refolding

Y Minami et al. J Biol Chem. 2000.

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Abstract

The 90-kDa heat shock protein, Hsp90, was previously shown to capture firefly luciferase during thermal inactivation and prevent it from undergoing an irreversible off-pathway aggregation, thereby maintaining it in a folding-competent state. While Hsp90 by itself was not sufficient to refold the denatured luciferase, addition of rabbit reticulocyte lysate remarkably restored the luciferase activity. Here we demonstrate that Hsc70, Hsp40, and the 20 S proteasome activator PA28 are the effective components in reticulocyte lysate. Purified Hsc70, Hsp40, and PA28 were necessary and sufficient to fully reconstitute Hsp90-initiated refolding. Kinetics of substrate binding support the idea that PA28 acts as the molecular link between the Hsp90-dependent capture of unfolded proteins and the Hsc70- and ATP-dependent refolding process.

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