Properties of the nuclear proteasome activator PA28gamma (REGgamma).
PA28 or 11S REG is a proteasome activator composed of homologous alpha- and beta-subunits and predominantly found in the cytosol. A homologous protein originally known as the Ki antigen but now called PA28gamma or REGgamma is predominantly localized in the nucleus. To further characterize the biochemical properties of PA28gamma, we expressed and purified homogenous recombinant human protein with and without an N-terminal 6-His extension. PA28gamma is a heptamer based on the molecular masses of the native and monomeric proteins. The heptameric 6-His fusion protein can dimerize. Recombinant PA28y stimulates the proteasome-mediated hydrolysis of synthetic substrates containing hydrophobic, basic, and acidic amino acids in the P1 position. Stimulation is dependent on substrate size. PA28y only minimally stimulates degradation of the oxidized B chain of insulin. PA28gamma may facilitate the later stages of protein metabolism in the nucleus and/or have a more specialized role in controlling the levels of biologically active peptides in the nucleus.
Wilk
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Department of Pharmacology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Chen
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Magnusson
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RP
D000818:Animals; D001324:Autoantigens; D002417:Cattle; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002918:Chymotrypsin / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000737:chemistry*; D003600:Cytosol / Q000378:metabolism*; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007328:Insulin / Q000378:metabolism; D009097:Multienzyme Complexes / Q000737:chemistry*; D009124:Muscle Proteins; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010902:Pituitary Gland / Q000737:chemistry; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000737:chemistry*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism
D001324:Autoantigens; D007328:Insulin; C099558:Ki antigen; D009097:Multienzyme Complexes; D009124:Muscle Proteins; D009687:Nuclear Proteins; C085047:PSME1 protein, human; D011506:Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D002918:Chymotrypsin; D014357:Trypsin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D010100:Oxygen