title: IRF-1 mediates upregulation of LMP7 by IFN-gamma and concerted expression of immunosubunits of the proteasome.
abstract: 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.
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Namiki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakamura
authors.forename: Shigeru
authors.initials: S
authors.lastname: Oshima
authors.forename: Motomi
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sekine
authors.forename: Kiichiro
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Okamoto
authors.forename: Takanori
authors.initials: T
authors.lastname: Kanai
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
mesh_terms: 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*
chemical_list: 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