Emerging roles of immunoproteasomes beyond MHC class I antigen processing

Cell Mol Life Sci. 2012 Aug;69(15):2543-58. doi: 10.1007/s00018-012-0938-0. Epub 2012 Mar 2.


The proteasome is a multi-catalytic protein complex whose primary function is the degradation of abnormal or foreign proteins. Upon exposure of cells to interferons (IFNs), the β1i/LMP2, β2i/MECL-1, and β5i/LMP7 subunits are induced and incorporated into newly synthesized immunoproteasomes (IP), which are thought to function solely as critical players in the optimization of the CD8(+) T-cell response. However, the observation that IP are present in several non-immune tissues under normal conditions and/or following pathological events militates against the view that its role is limited to MHC class I presentation. In support of this concept, the recent use of genetic models deficient for β1i/LMP2, β2i/MECL-1, or β5i/LMP7 has uncovered unanticipated functions for IP in innate immunity and non-immune processes. Herein, we review recent data in an attempt to clarify the role of IP beyond MHC class I epitope presentation with emphasis on its involvement in the regulation of protein homeostasis, cell proliferation, and cytokine gene expression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigen Presentation
  • Cell Proliferation
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Gene Expression Regulation
  • Histocompatibility Antigens Class I / metabolism
  • Homeostasis
  • Humans
  • Immunity, Innate
  • Inflammation / immunology
  • Inflammation / metabolism
  • Proteasome Endopeptidase Complex / chemistry
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / immunology*
  • Proteasome Endopeptidase Complex / physiology*
  • Proteins / metabolism
  • Signal Transduction
  • Stress, Physiological


  • Cytokines
  • Histocompatibility Antigens Class I
  • Proteins
  • Proteasome Endopeptidase Complex