INTERFERON-GAMMA INDUCES DIFFERENT SUBUNIT ORGANIZATIONS AND FUNCTIONAL DIVERSITY OF PROTEASOMES
INTERFERON-GAMMA INDUCES DIFFERENT SUBUNIT ORGANIZATIONS AND FUNCTIONAL DIVERSITY OF PROTEASOMES
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DOI：
10.1093/oxfordjournals.jbchem.a124327
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发表时间：
1994-02-01
影响因子：
2.7
通讯作者：
ICHIHARA, A
中科院分区：
文献类型：
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作者：
AKI, M;SHIMBARA, N;ICHIHARA, A
为了获得蛋白酶体在免疫系统中的作用的信息，我们研究了一个主要的免疫调节细胞因子，γ干扰素（IFN-γ），蛋白酶体的表达，结构和功能的影响。IFN-γ极大地增加了编码LMP 2和LMP 7的mRNA的水平，LMP 2和LMP 7是由II类MHC区域内的基因编码的假定的免疫蛋白酶体亚基，并且合成的这两个亚基在各种类型的人类细胞中完全组装成蛋白酶体多亚基复合物。蛋白酶体的亚基组织响应于IFN-γ刺激而改变，这是由于通过至少6个蛋白酶体基因（包括LMP 2/LMP 7）的上调和下调表达而组装新合成的亚基，而不改变预先存在的蛋白酶体的结构。有趣的是，IFN-γ显著刺激多功能蛋白酶体的胰蛋白酶样和胰凝乳蛋白酶样活性，并抑制肽酰谷氨酰肽水解活性，而不影响ATP-，泛素非依赖性蛋白水解的活性。这些结果表明，IFN-γ不仅改变蛋白酶体的结构组织，而且还改变其功能。基于这些发现，我们讨论了在抗原处理/呈递途径的蛋白酶体的功能多样性，通过改变其亚基组装响应IFN-γ刺激获得的作用。
To obtain information on the role of proteasomes in the immune system, we examined the effect of a major immunomodulatory cytokine, gamma interferon (IFN-gamma), on the expressions, structures, and functions of proteasomes. IFN-gamma greatly increased the levels of the mRNAs encoding LMP2 and LMP7, putative immuno-proteasome subunits encoded by genes within the class II MHC region, and these two subunits synthesized were assembled completely into the proteasomal multi-subunit complex in various types of human cells. The subunit organization of the proteasome changed in response to IFN-gamma stimulation, due to assembly of newly synthesized subunits through up- and down-expressions of at least 6 proteasome genes including LMP2/LMP7 without change in the structure of pre-existing proteasomes. Interestingly, IFN-gamma dramatically stimulated the trypsin-like and chymotrypsin-like activities of the multifunctional proteasome and depressed the peptidylglutamyl-peptide-hydrolyzing activity, without affecting the activity for ATP-, ubiquitindependent proteolysis. These results indicate that IFN-gamma modifies not only the structural organization of the proteasome, but also its functions. Based on these findings, we discuss the role in the antigen processing/presentation pathway of proteasomes with functional diversity acquired through alteration of their subunit assembly in response to IFN-gamma stimulation.