Phosphorylation of CIITA directs its oligomerization, accumulation and increased activity on MHCII promoters

EMBO J. 2002 Oct 15;21(20):5467-76. doi: 10.1093/emboj/cdf557.

Abstract

The class II transactivator (CIITA) is the master regulator of major histocompatibility complex class II (MHCII) transcription. Its activity is regulated at the post-transcriptional level by phosphorylation and oligomerization. This aggregation mapped to and depended on the phosphorylation of residues between positions 253 and 321 in CIITA, which resulted in a dramatic accumulation of the protein and increased expression of MHCII genes in human promonocytic U937 cells, which represent immature antigen-presenting cells. Thus, the post-transcriptional modification of CIITA plays an important role in the immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cytoplasm / drug effects
  • Cytoplasm / metabolism
  • Gene Expression
  • Genes, MHC Class II*
  • Humans
  • Nuclear Proteins*
  • Phosphorylation
  • Promoter Regions, Genetic
  • Protein Processing, Post-Translational
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Deletion
  • Temperature
  • Tetradecanoylphorbol Acetate / pharmacology
  • Trans-Activators / chemistry
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transfection
  • U937 Cells

Substances

  • MHC class II transactivator protein
  • Nuclear Proteins
  • Recombinant Proteins
  • Trans-Activators
  • Tetradecanoylphorbol Acetate