title: gamma-Interferon decreases the level of 26 S proteasomes and changes the pattern of phosphorylation.
abstract: In mammalian cells proteasomes can be activated by two different types of regulatory complexes which bind to the ends of the proteasome cylinder. Addition of two 19 S (PA700; ATPase) complexes forms the 26 S proteasome, which is responsible for ATP-dependent non-lysosomal degradation of intracellular proteins, whereas 11 S complexes (PA28; REG) have been implicated in antigen processing. The PA28 complex is upregulated in response to gamma-interferon (gamma-IFN) as are three non-essential subunits of the 20 S proteasome. In the present study we have investigated the effects of gamma-IFN on the level of different proteasome complexes and on the phosphorylation of proteasome subunits. After treatment of cells with gamma-IFN, the level of 26 S proteasomes decreased and there was a concomitant increase in PA28-proteasome complexes. However, no free 19 S regulatory complexes were detected. The majority of the gamma-IFN-inducible proteasome subunits LMP2 and LMP7 were present in PA28-proteasome complexes, but these subunits were also found in 26 S proteasomes. The level of phosphorylation of both 20 S and 26 S proteasome subunits was found to decrease after gamma-IFN treatment of cells. The C8 alpha subunit showed more than a 50% decrease in phosphorylation, and the phosphorylation of C9 was only barely detectable after gamma-IFN treatment. These results suggest that association of regulatory components to 20 S proteasomes is regulated, and that phosphorylation of proteasome alpha subunits may be one mode of regulation.
authors.affiliation: Department of Biochemistry, University of Bristol, School of Medical Sciences, Bristol BS8 1TD, U.K.
authors.forename: S
authors.initials: S
authors.lastname: Bose
authors.forename: P
authors.initials: P
authors.lastname: Brooks
authors.forename: G G
authors.initials: GG
authors.lastname: Mason
authors.forename: A J
authors.initials: AJ
authors.lastname: Rivett
mesh_terms: D002460:Cell Line; D002850:Chromatography, Gel; D015536:Down-Regulation; D006801:Humans; D015151:Immunoblotting; D007371:Interferon-gamma / Q000494:pharmacology*; D008956:Models, Chemical; D009124:Muscle Proteins; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D009124:Muscle Proteins; C085047:PSME1 protein, human; D011506:Proteins; D007371:Interferon-gamma; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease