gamma-Interferon decreases the level of 26 S proteasomes and changes the pattern of phosphorylation

Biochem J. 2001 Jan 15;353(Pt 2):291-7. doi: 10.1042/0264-6021:3530291.


In mammalian cells proteasomes can be activated by two different types of regulatory complexes which bind to the ends of the proteasome cylinder. Addition of two 19 S (PA700; ATPase) complexes forms the 26 S proteasome, which is responsible for ATP-dependent non-lysosomal degradation of intracellular proteins, whereas 11 S complexes (PA28; REG) have been implicated in antigen processing. The PA28 complex is upregulated in response to gamma-interferon (gamma-IFN) as are three non-essential subunits of the 20 S proteasome. In the present study we have investigated the effects of gamma-IFN on the level of different proteasome complexes and on the phosphorylation of proteasome subunits. After treatment of cells with gamma-IFN, the level of 26 S proteasomes decreased and there was a concomitant increase in PA28-proteasome complexes. However, no free 19 S regulatory complexes were detected. The majority of the gamma-IFN-inducible proteasome subunits LMP2 and LMP7 were present in PA28-proteasome complexes, but these subunits were also found in 26 S proteasomes. The level of phosphorylation of both 20 S and 26 S proteasome subunits was found to decrease after gamma-IFN treatment of cells. The C8 alpha subunit showed more than a 50% decrease in phosphorylation, and the phosphorylation of C9 was only barely detectable after gamma-IFN treatment. These results suggest that association of regulatory components to 20 S proteasomes is regulated, and that phosphorylation of proteasome alpha subunits may be one mode of regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Chromatography, Gel
  • Down-Regulation
  • Humans
  • Immunoblotting
  • Interferon-gamma / pharmacology*
  • Models, Chemical
  • Muscle Proteins*
  • Peptide Hydrolases / chemistry
  • Peptide Hydrolases / metabolism*
  • Phosphorylation
  • Proteasome Endopeptidase Complex*
  • Proteins / chemistry
  • Proteins / metabolism


  • Muscle Proteins
  • PSME1 protein, human
  • Proteins
  • Interferon-gamma
  • Peptide Hydrolases
  • Proteasome Endopeptidase Complex
  • ATP dependent 26S protease