RRC ID 42307
著者 Tanioka T, Hattori A, Mizutani S, Tsujimoto M.
タイトル Regulation of the human leukocyte-derived arginine aminopeptidase/endoplasmic reticulum-aminopeptidase 2 gene by interferon-gamma.
ジャーナル FEBS J
Abstract 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.
巻・号 272(4)
ページ 916-28
公開日 2005-2-1
DOI 10.1111/j.1742-4658.2004.04521.x
PII EJB4521
PMID 15691326
MeSH Aminopeptidases / genetics* Aminopeptidases / metabolism Base Sequence Gene Expression Regulation / physiology* Humans Interferon-gamma / metabolism* Jurkat Cells Molecular Sequence Data Promoter Regions, Genetic Sequence Analysis, DNA Time Factors
IF 4.392
引用数 22
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 Jurkat(RCB0806)