title: Newly identified pair of proteasomal subunits regulated reciprocally by interferon gamma.
abstract: Interferon (IFN) gamma induces replacements of the proteasomal subunits X and Y by LMP7 and LMP2, respectively, resulting in an alteration of the proteolytic specificity. We found a third pair of proteasome subunits expressed reciprocally in response to IFN-gamma. Molecular cloning of a cDNA encoding one subunit designated as Z, downregulated by IFN-gamma, showed that it is a novel proteasomal subunit with high homology to MECL1, which is markedly induced by IFN-gamma. Thus, IFN-gamma induces subunit replacements of not only X and Y by LMP7 and LMP2, respectively, but also of Z by MECL1, producing proteasomes responsible for immunological processing of endogenous antigens. When processed from their precursors, three pairs of the 10 homologous, but distinct, beta-type subunits of eukaryotic proteasomes, that is, X/LMP7, Y/LMP2, and Z/MECL1, have an NH2-terminal threonine residue, assumed to be part of a catalytic center. These findings suggest that the altered molecular organization of the proteasome induced by IFN-gamma may be responsible for acquisition of its functional change.
authors.affiliation: Institute for Enzyme Research, University of Tokushima, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hisamatsu
authors.forename: N
authors.initials: N
authors.lastname: Shimbara
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: P
authors.initials: P
authors.lastname: Kristensen
authors.forename: K B
authors.initials: KB
authors.lastname: Hendil
authors.forename: T
authors.initials: T
authors.lastname: Fujiwara
authors.forename: E
authors.initials: E
authors.lastname: Takahashi
authors.forename: N
authors.initials: N
authors.lastname: Tanahashi
authors.forename: T
authors.initials: T
authors.lastname: Tamura
authors.forename: A
authors.initials: A
authors.lastname: Ichihara
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation; D001483:Base Sequence; D002871:Chromosome Banding; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007371:Interferon-gamma / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D046988:Proteasome Endopeptidase Complex; D014176:Protein Biosynthesis; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D017386:Sequence Homology, Amino Acid
chemical_list: D009097:Multienzyme Complexes; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; C098949:proteasome subunit Z; C098948:PSMB10 protein, human; C088874:PSMB5 protein, human; C088875:PSMB6 protein, human; D046988:Proteasome Endopeptidase Complex