Interferon-gamma induces different subunit organizations and functional diversity of proteasomes

J Biochem. 1994 Feb;115(2):257-69. doi: 10.1093/oxfordjournals.jbchem.a124327.


To obtain information on the role of proteasomes in the immune system, we examined the effect of a major immunomodulatory cytokine, gamma interferon (IFN-gamma), on the expressions, structures, and functions of proteasomes. IFN-gamma greatly increased the levels of the mRNAs encoding LMP2 and LMP7, putative immuno-proteasome subunits encoded by genes within the class II MHC region, and these two subunits synthesized were assembled completely into the proteasomal multi-subunit complex in various types of human cells. The subunit organization of proteasome changed in response to IFN-gamma stimulation, due to assembly of newly synthesized subunits through up- and down-expressions of at least 6 proteasome genes including LMP2/LMP7 without change in the structure of pre-existing proteasomes. Interestingly, IFN-gamma dramatically stimulated the trypsin-like and chymotrypsin-like activities of the multifunctional proteasome and depressed the peptidylglutamyl-peptide-hydrolyzing activity, without affecting the activity for ATP-, ubiquitin-dependent proteolysis. These results indicate that IFN-gamma modifies not only the structural organization of the proteasome, but also its functions. Based on these findings, we discuss the role in the antigen processing/presentation pathway of proteasomes with functional diversity acquired through alteration of their subunit assembly in response to IFN-gamma stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Amino Acid Sequence
  • Colonic Neoplasms
  • Cysteine Endopeptidases / chemistry
  • Cysteine Endopeptidases / metabolism*
  • Flow Cytometry
  • Histocompatibility Antigens Class I / biosynthesis
  • Histocompatibility Antigens Class I / genetics
  • Humans
  • Hydrolysis
  • Interferon-gamma / pharmacology*
  • Leukemia, Myeloid
  • Major Histocompatibility Complex / drug effects
  • Molecular Sequence Data
  • Multienzyme Complexes / chemistry
  • Multienzyme Complexes / metabolism*
  • Nucleic Acid Hybridization
  • Proteasome Endopeptidase Complex
  • Proteins / chemistry
  • Proteins / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins
  • Tumor Cells, Cultured
  • Ubiquitins / pharmacology


  • Histocompatibility Antigens Class I
  • Multienzyme Complexes
  • Proteins
  • RNA, Messenger
  • Recombinant Proteins
  • Ubiquitins
  • LMP-2 protein
  • Interferon-gamma
  • Adenosine Triphosphate
  • Cysteine Endopeptidases
  • LMP7 protein
  • Proteasome Endopeptidase Complex