Heat shock protein-90 and the catalytic activities of the 20 S proteasome (multicatalytic proteinase complex).
The effect of heat shock protein 90 (Hsp-90) and several other proteins on the catalytic activities of the 20 S proteasome (MPC) was examined. The chymotrypsin-like (ChT-L) and peptidylglutamyl-peptide hydrolyzing (PGPH) activities of the pituitary MPC were inhibited by Hsp-90 with IC50 values of 8 and 28 nM, respectively. Bovine serum albumin and two other proteins tested inhibited the same activities with much higher IC50 values. The trypsin-like and branched-chain amino-acid-preferring activities were not affected by any of the proteins. None of the activities of the bovine spleen MPC, an enzyme form in which the X, Y, and Z subunits are virtually completely replaced by the LMP2, LMP7, and LMP10 subunits, was affected by either Hsp-90 or the other proteins tested. Hsp-90 inhibited the degradation of the oxidized B-chain of insulin by the pituitary MPC but not by its spleen counterpart. The PA28 activator (11 S regulator; REG) of the proteasome abolished the inhibitory effect of Hsp-90 and other proteins on the ChT-L and PGPH activities of the pituitary MPC. It is suggested that Hsp-90 induces conformational changes that affect the ChT-L and PGPH activities expressed by the X and Y subunits, respectively, but does not affect the activities expressed by LMP subunits.
Lu
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Department of Pharmacology, Mount Sinai School of Medicine of the City, University of New York, New York 10029, USA.
Michaud
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Orlowski
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D000818:Animals; D002417:Cattle; D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D010047:Ovalbumin / Q000494:pharmacology; D010902:Pituitary Gland / Q000201:enzymology; D011480:Protease Inhibitors / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000494:pharmacology; D012259:Ribonuclease, Pancreatic / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013154:Spleen / Q000201:enzymology
D018841:HSP90 Heat-Shock Proteins; D007328:Insulin; D009097:Multienzyme Complexes; D011480:Protease Inhibitors; D011506:Proteins; D012710:Serum Albumin, Bovine; D010047:Ovalbumin; D012259:Ribonuclease, Pancreatic; D010450:Endopeptidases; D002918:Chymotrypsin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C114177:peptidylglutamylpeptide hydrolase