Newly identified pair of proteasomal subunits regulated reciprocally by interferon gamma.
Newly identified pair of proteasomal subunits regulated reciprocally by interferon gamma.
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DOI：
10.1084/jem.183.4.1807
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发表时间：
1996-04-01
期刊：
影响因子：
--
通讯作者：
Tanaka K
中科院分区：
文献类型：
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作者：
Hisamatsu H;Shimbara N;Saito Y;Kristensen P;Hendil KB;Fujiwara T;Takahashi E;Tanahashi N;Tamura T;Ichihara A;Tanaka K
干扰素（IFN）γ诱导蛋白酶体亚基X和Y分别被LMP 7和LMP 2替换，导致蛋白水解特异性的改变。我们发现第三对蛋白酶体亚基在IFN-γ的作用下表达β 2。分子克隆的cDNA编码一个亚基命名为Z，下调IFN-γ，表明它是一个新的蛋白酶体亚基与MECL 1，这是显着诱导IFN-γ具有高度同源性。因此，IFN-γ不仅诱导X和Y分别被LMP 7和LMP 2的亚基置换，而且诱导Z被MECL 1的亚基置换，产生负责内源性抗原的免疫加工的蛋白酶体。当从它们的前体加工时，真核蛋白酶体的10个同源但不同的β型亚基中的三对，即X/LMP 7、Y/LMP 2和Z/MECL 1，具有NH 2-末端苏氨酸残基，被认为是催化中心的一部分。这些发现表明IFN-γ诱导的蛋白酶体分子结构的改变可能是其功能改变的原因。
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.