PEPTIDASE ACTIVITIES OF PROTEASOMES ARE DIFFERENTIALLY REGULATED BY THE MAJOR HISTOCOMPATIBILITY COMPLEX-ENCODED GENES FOR LMP2 AND LMP7
PEPTIDASE ACTIVITIES OF PROTEASOMES ARE DIFFERENTIALLY REGULATED BY THE MAJOR HISTOCOMPATIBILITY COMPLEX-ENCODED GENES FOR LMP2 AND LMP7
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DOI：
10.1073/pnas.91.20.9213
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发表时间：
1994-09-27
影响因子：
11.1
通讯作者：
GOLDBERG, AL
中科院分区：
文献类型：
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作者：
GACZYNSKA, M;ROCK, KL;GOLDBERG, AL
最近的研究表明，蛋白酶体与抗原肽的产生有关，这些抗原肽以主要组织相容性复合体I类分子的形式呈现给T淋巴细胞。干扰素γ改变蛋白酶体的亚基组成，并引起其肽酶活性的变化，这应该有利于产生具有疏水性或碱性羧基末端的肽（即在主要组织相容性复合体I类分子上发现的类型）。有人提出，肽酶活性的这些变化是由于干扰素诱导的主要组织相容性复合物编码亚基LMP2和-7被纳入蛋白酶体。通过将LMP7基因转染到淋巴母细胞或HeLa细胞，我们发现LMP7增加了20S和26S蛋白酶体切割疏水性和碱性残基后肽的能力（V-max），而不影响酸性残基后的水解。这些变化取决于纳入蛋白酶体的LMP7亚基的数量。转染LMP2减少了酸性残基后多肽的裂解，增加了碱性残基后的水解，并且不影响疏水活性。由于仅在少量LMP2或-7掺入后总蛋白酶体群的活性就发生了变化，因此这些亚基一定会引起肽酶活性的重大改变。因此，它们的表达可以解释干扰素诱导的蛋白酶体活性的变化，这些发现进一步支持了LMPs在改变抗原呈递产生的肽的性质方面的作用。
Recent studies have implicated proteasomes in the generation of the antigenic peptides that are presented on major histocompatibility complex class I molecules to T lymphocytes. Interferon gamma modifies the subunit composition of proteasomes and causes changes in their peptidase activities that should favor the production of peptides with hydrophobic or basic carboxyl termini (i.e., the types found on major histocompatibility complex class I molecules). It has been proposed that these changes in peptidase activity are due to incorporation into proteasomes of the major histocompatibility complex-encoded subunits LMP2 and -7, which are induced by interferon gamma. Here we show by gene transfection into lymphoblasts or HeLa cells that LMP7 increases the capacity (V-max) of 20S and 26S proteasomes to cleave peptides after hydrophobic and basic residues without affecting hydrolysis after acidic residues. These changes depended on the amount of LMP7 subunits incorporated into proteasomes. Transfection of LMP2 reduced cleavage of peptides after acidic residues, increased hydrolysis after basic residues, and did not affect the hydrophobic activity. Since the activity of the total proteasome population changed after incorporation of only small amounts of LMP2 or -7, these subunits must cause major alterations in peptidase activity. Thus, their expression can account for the changes in proteasome activity induced by interferon gamma, and these findings lend further support to the proposed roles of LMPs in altering the nature of the peptides generated for antigen presentation.