Age-dependent association of isolated bovine lens multicatalytic proteinase complex (proteasome) with heat-shock protein 90, an endogenous inhibitor.
The multicatalytic proteinase complex (MPC) (proteasome) is a high-molecular-weight proteolytic enzyme found in eukaryotic cells and archaebacteria. Regulatory proteins that inhibit or activate the MPC have been described. Association with an ATPase complex alters the specificity of the multicatalytic proteinase complex to permit cleavage of ubiquitinylated proteins. Unidentified proteins have been observed in highly purified preparations of the multicatalytic proteinase complex. Based on immunoreactivity and N-terminal sequencing, we have identified heat-shock protein 90 as a major component of the multicatalytic proteinase complex prepared from 1-month, but not 2-year bovine lenses. alpha-Crystallin, a lens structural protein with chaperone activity, is also found in multicatalytic proteinase complex preparations. Both heat-shock protein 90 and alpha-crystallin inhibit hydrolysis of Cbz-Leu-Leu-Leu-MCA by the multicatalytic proteinase complex at a stoichiometry of 1 mol heat-shock protein per mole of MPC. Heat-shock proteins may interact with denatured proteins and facilitate their degradation. These studies give evidence for the involvement of heat-shock proteins in proteolysis by direct interaction with the multicatalytic proteinase complex.
D000367:Age Factors; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D003459:Crystallins / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D007908:Lens, Crystalline / Q000378:metabolism; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009097:Multienzyme Complexes / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding
D003459:Crystallins; D004791:Enzyme Inhibitors; D018841:HSP90 Heat-Shock Proteins; D046911:Macromolecular Substances; D009097:Multienzyme Complexes; D010455:Peptides; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex