Properties of the nuclear proteasome activator PA28γ (REG γ)

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 PA28 gamma or REG gamma is predominantly localized in the nucleus. To further characterize the biochemical properties of PA28 gamma, we expressed and purified homogenous recombinant human protein with and without an N-terminal 6-His extension. PA28 gamma is a heptamer based on the molecular masses of the native and monomeric proteins. The heptameric 6-His fusion protein can dimerize. Recombinant PA28 gamma stimulates the proteasome-mediated hydrolysis of synthetic substrates containing hydrophobic, basic, and acidic amino acids in the pi position, Stimulation is dependent on substrate size. PA28 gamma only minimally stimulates degradation of the oxidized B chain of insulin. PA28 gamma 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. (C) 2000 Academic Press.