Newly identified pair of proteasomal subunits regulated reciprocally by interferon gamma.
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.
Hisamatsu
H
H
Institute for Enzyme Research, University of Tokushima, Japan.
Shimbara
N
N
Saito
Y
Y
Kristensen
P
P
Hendil
K B
KB
Fujiwara
T
T
Takahashi
E
E
Tanahashi
N
N
Tamura
T
T
Ichihara
A
A
Tanaka
K
K
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
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