IRF-1 mediates upregulation of LMP7 by IFN-gamma and concerted expression of immunosubunits of the proteasome.
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-gamma-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-gamma-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.
Namiki
Shin
S
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Japan.
Nakamura
Tetsuya
T
Oshima
Shigeru
S
Yamazaki
Motomi
M
Sekine
Yuko
Y
Tsuchiya
Kiichiro
K
Okamoto
Ryuichi
R
Kanai
Takanori
T
Watanabe
Mamoru
M
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000502:physiology*; D051379:Mice; D009097:Multienzyme Complexes / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D015854:Up-Regulation / Q000502:physiology*
D017931:DNA Primers; D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D009097:Multienzyme Complexes; D010750:Phosphoproteins; D012333:RNA, Messenger; D007371:Interferon-gamma; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex