| RRC ID |
42307
|
| Author |
Tanioka T, Hattori A, Mizutani S, Tsujimoto M.
|
| Title |
Regulation of the human leukocyte-derived arginine aminopeptidase/endoplasmic reticulum-aminopeptidase 2 gene by interferon-gamma.
|
| Journal |
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.
|
| Volume |
272(4)
|
| Pages |
916-28
|
| Published |
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
|
| Times Cited |
22
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Human and Animal Cells |
Jurkat(RCB0806) |
