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首页> 外文期刊>The FEBS journal >Regulation of the human leukocyte-derived arginine aminopeptidase/endoplasmic reticulum-aminopeptidase 2 gene by interferon-gamma
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Regulation of the human leukocyte-derived arginine aminopeptidase/endoplasmic reticulum-aminopeptidase 2 gene by interferon-gamma

机译：干扰素-γ对人白细胞衍生的精氨酸氨基肽酶/内质网-氨基肽酶2基因的调控

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摘要

The leukocyte-derived arginine aminopeptidase (L-RAP) is the second aminopeptidase localized in the endoplasmic reticulum (ER) processing antigenic peptides presented to major histocompatibility complex (MHC) class I molecules. In this study, the genomic organization of the gene encoding human L-RAP was determined and the regulatory mechanism of its expression was elucidated. The entire genomic structure of the L-RAP gene is similar to both placental leucine aminopeptidase (P-LAP) and adipocyte-derived leucine aminopeptidase (A-LAP) genes, confirming the close relationship of these three enzymes. Interferon (IFN)-gamma up-regulates the expression of the L-RAP gene. Deletion and site-directed mutagenic analyses of the 5'-flanking region of the L-RAP gene and electrophoretic mobility shift assay indicated that while interferon regulatory factor (IRF)-2 is important in the basal condition, IRF-1 is the primary regulator of IFN-gamma-mediated augmentation of the gene expression. In addition, PU.1, a member of the E26 transformation-specific family of transcription factors, also plays a role in the regulation of gene expression. The maximum expression of the gene was achieved by coexpression of IRF-1 and PU.1 in HEK293 cells and IRF-2 suppressed the IRF-1-mediated enhancement of gene expression, suggesting that IFN-gamma-induced L-RAP gene expression is cooperatively regulated by IRFs and PU.1 transcription factors.
机译：白细胞衍生的精氨酸氨基肽酶（L-RAP）是位于内质网（ER）处理抗原肽中的第二个氨基肽酶，该肽呈递给主要组织相容性复合体（MHC）I类分子。在这项研究中，确定了编码人L-RAP的基因的基因组结构，并阐明了其表达的调控机制。 L-RAP基因的整个基因组结构与胎盘亮氨酸氨基肽酶（P-LAP）和脂肪细胞衍生的亮氨酸氨基肽酶（A-LAP）基因相似，证实了这三种酶的密切关系。干扰素（IFN）-γ上调L-RAP基因的表达。 L-RAP基因5'侧翼区的缺失和定点诱变分析以及电泳迁移率迁移分析表明，在基础条件下，干扰素调节因子（IRF）-2是重要的，而IRF-1是主要调节剂-γ介导的基因表达增强。此外，PU.1是E26转化特异性转录因子家族的成员，在基因表达的调节中也发挥着作用。该基因的最大表达是通过在HEK293细胞中共表达IRF-1和PU.1来实现的，而IRF-2抑制了IRF-1介导的基因表达的增强，表明IFN-γ诱导的L-RAP基因表达为由IRF和PU.1转录因子协同调控。

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