Role of Sug1, a 19S proteasome ATPase, in the transcription of MHC I and the atypical MHC II molecules, HLA-DM and HLA-DO

Immunol Lett. 2012 Sep;147(1-2):67-74. doi: 10.1016/j.imlet.2012.06.005. Epub 2012 Jul 4.

Abstract

The 19S proteasome regulatory particle plays a critical role in cellular proteolysis. However, emerging evidence suggests roles for 19S proteasome subunits in regulating yeast and mammalian transcription. It has been previously shown that Sug1 is important for the transcription of MHC II molecules. We report here that Sug1 also has a role in regulating transcription of class I MHC and the MHC II-like molecules, HLA-DM and HLA-DO. Reduction of Sug1 expression causes a decrease in the transcription of MHC I and MHC II-like molecules. In addition, we show that association of Sug1 with MHC promoters is followed by the recruitment of the CREB-binding protein (CBP) and the class II transactivator (CIITA). Reduction of Sug1 expression is accompanied by decreased recruitment of CBP and CIITA to the MHC promoters and decreased histone H3 acetylation in these promoters. These studies suggest that Sug1 plays a critical role in transcription of MHC class I, and the MHC class II-like molecules, HLA-DM and HLA-DO.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Acetylation / drug effects
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • CREB-Binding Protein / metabolism
  • Cell Line
  • Gene Expression Regulation / drug effects
  • HLA-D Antigens / genetics*
  • Histocompatibility Antigens Class I / genetics*
  • Histones / metabolism
  • Humans
  • Interferon-gamma / pharmacology
  • LIM Domain Proteins / genetics
  • LIM Domain Proteins / metabolism*
  • Nuclear Proteins / metabolism
  • Promoter Regions, Genetic
  • Proteasome Endopeptidase Complex
  • RNA Interference
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic* / drug effects

Substances

  • Adaptor Proteins, Signal Transducing
  • HLA-D Antigens
  • HLA-DM antigens
  • HLA-DO antigens
  • Histocompatibility Antigens Class I
  • Histones
  • LIM Domain Proteins
  • MHC class II transactivator protein
  • Nuclear Proteins
  • PSMC5 protein, human
  • Trans-Activators
  • Transcription Factors
  • Interferon-gamma
  • CREB-Binding Protein
  • Proteasome Endopeptidase Complex
  • ATPases Associated with Diverse Cellular Activities