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IRF‐1 mediates upregulation of LMP7 by IFN‐γ and concerted expression of immunosubunits of the proteasome
Author(s) -
Namiki Shin,
Nakamura Tetsuya,
Oshima Shigeru,
Yamazaki Motomi,
Sekine Yuko,
Tsuchiya Kiichiro,
Okamoto Ryuichi,
Kanai Takanori,
Watanabe Mamoru
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.04.012
Subject(s) - irf1 , proteasome , downregulation and upregulation , transcription factor , microbiology and biotechnology , interferon , master regulator , protein subunit , biology , small interfering rna , major histocompatibility complex , transcription (linguistics) , mhc class i , regulator , rna , genetics , gene , linguistics , philosophy
An immunoproteasome subunit low molecular weight protein 7 (LMP7) plays critical roles in major histocompatibility complex class I antigen processing; however, the mechanism for its expression has remained unclear. We demonstrate that interferon (IFN) regulatory factor‐1 (IRF‐1) has a pivotal role in IFN‐γ‐dependent LMP7 expression, as was shown for the other two immunosubunits. A tetracycline‐inducible system for IRF‐1 revealed its function in the LMP7 expression, and a genomic region functionally interacting with IRF‐1 was also determined. Furthermore, the role of IRF‐1 in IFN‐γ‐inducible LMP7 transcription was confirmed by employing small interfering RNA experiments and IRF‐1−/− mice. These results suggest that IRF‐1 acts as a master regulator for the concerted expression of immunoproteasome components.