IRF-1 mediates upregulation of LMP7 by IFN-gamma and concerted expression of immunosubunits of the proteasome

FEBS Lett. 2005 May 23;579(13):2781-7. doi: 10.1016/j.febslet.2005.04.012. Epub 2005 Apr 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • DNA Primers
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Humans
  • Interferon Regulatory Factor-1
  • Interferon-gamma / physiology*
  • Mice
  • Multienzyme Complexes / physiology*
  • Phosphoproteins / genetics
  • Phosphoproteins / physiology*
  • Proteasome Endopeptidase Complex / metabolism*
  • RNA, Messenger / genetics
  • Up-Regulation / physiology*

Substances

  • DNA Primers
  • DNA-Binding Proteins
  • IRF1 protein, human
  • Interferon Regulatory Factor-1
  • Irf1 protein, mouse
  • Multienzyme Complexes
  • Phosphoproteins
  • RNA, Messenger
  • Interferon-gamma
  • LMP7 protein
  • Proteasome Endopeptidase Complex