Properties of the nuclear proteasome activator PA28 gamma (REG gamma)

PA28 or 11S REG; is a proteasome activator composed of homologous alpha- an d beta -subunits and predominantly found in the cytosol. A homologous prote in originally known as the Ki antigen but now called PA28 gamma or REG gamm a is predominantly localized in the nucleus. To further characterize the bi ochemical properties of PA28 gamma, we expressed and purified homogenous re combinant human protein with and without an N-terminal 6-His extension. PA2 8 gamma is a heptamer based on the molecular masses of the native and monom eric proteins. The heptameric 6-His fusion protein can dimerize. Recombinan t PA28 gamma stimulates the proteasome-mediated hydrolysis of synthetic sub strates containing hydrophobic, basic, and acidic amino acids in the pi pos ition, Stimulation is dependent on substrate size. PA28 gamma only minimall y stimulates degradation of the oxidized B chain of insulin. PA28 gamma may facilitate the later stages of protein metabolism in the nucleus and/or ha ve a more specialized role in controlling the levels of biologically active peptides in the nucleus. (C) 2000 Academic Press.