GTP-dependent recruitment of CIITA to the class II major histocompatibility complex promoter

J Biol Chem. 2007 Sep 7;282(36):26178-84. doi: 10.1074/jbc.M611747200. Epub 2007 Jul 10.

Abstract

We previously established that the class II transactivator CIITA binds GTP and disruption of the GTP binding ability of CIITA results in increased cytoplasmic CIITA, loss of nuclear CIITA, and thus diminished class II major histocompatibility complex transcription. Because of its role in facilitating nuclear localization, whether GTP binding is also required for CIITA-mediated transactivation of major histocompatibility class II genes remains unclear. We now show that recruitment of CIITA to the human leukocyte antigen (HLA)-DR promoter and activation of HLA-DR transcription is also GTP-dependent. After restoration of nuclear expression, CIITA mutants defective in GTP binding lack full transcriptional activation capacity. Although the availability of the activation domain of CIITA is unaltered, GTP mutants no longer cooperate with CREB-binding protein, p300, and pCAF and are defective in recruitment to the HLA-DR promoter.

Publication types

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

MeSH terms

  • Active Transport, Cell Nucleus / physiology
  • Animals
  • COS Cells
  • CREB-Binding Protein / genetics
  • CREB-Binding Protein / metabolism
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Chlorocebus aethiops
  • Cytoplasm / genetics
  • Cytoplasm / metabolism
  • Guanosine Triphosphate / genetics
  • Guanosine Triphosphate / metabolism*
  • HLA-DR Antigens / biosynthesis*
  • HLA-DR Antigens / genetics
  • HeLa Cells
  • Humans
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Promoter Regions, Genetic / physiology*
  • Protein Binding
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription, Genetic / physiology
  • Transcriptional Activation / physiology*
  • p300-CBP Transcription Factors / genetics
  • p300-CBP Transcription Factors / metabolism

Substances

  • HLA-DR Antigens
  • MHC class II transactivator protein
  • Nuclear Proteins
  • Trans-Activators
  • Guanosine Triphosphate
  • CREB-Binding Protein
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor