Properties of the beta subunit of the proteasome activator PA28 (11S REG).
The proteasome activator PA28 (11S REG) is composed of two homologous subunits termed alpha and beta. The properties of the recombinant beta-subunit were explored and compared to the properties of the recombinant alpha-subunit. PA28beta produced in an Escherichia coli expression system migrates on a calibrated gel filtration column as an apparent heptamer (Mr = 250,000). Low concentrations of SDS (0.005%), dissociate the protein to a monomer (Mr = 33,000). PA28beta, has a complex effect on proteasome activity. At concentrations which favor oligomerization (> 2 microM), PA28beta is a strong proteasome activator although its affinity for the proteasome is about 10-fold less than recombinant PA28alpha. The catalytic properties of the PA28alpha and PA28beta-activated proteasome are similar. At low concentrations, PA28beta is a monomer and a potent allosteric proteasome inhibitor. These studies show that oligomerization of PA28beta is required for proteasome activation and that PA28beta monomers are potent proteasome inhibitors.
Wilk
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Department of Pharmacology, Mount Sinai School of Medicine, New York, New York 10029, USA. sherwin.wilk@mssm.edu
Chen
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Magnusson
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D000494:Allosteric Regulation; D000818:Animals; D001704:Biopolymers / Q000378:metabolism; D002417:Cattle; D002918:Chymotrypsin / Q000737:chemistry; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D004789:Enzyme Activation; D004926:Escherichia coli; D018841:HSP90 Heat-Shock Proteins / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology
D001704:Biopolymers; D018841:HSP90 Heat-Shock Proteins; D009097:Multienzyme Complexes; D011506:Proteins; D011994:Recombinant Proteins; D010450:Endopeptidases; D002918:Chymotrypsin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C114177:peptidylglutamylpeptide hydrolase