Requirement for O-linked N-acetylglucosaminyltransferase in lymphocytes activation

EMBO J. 2007 Oct 17;26(20):4368-79. doi: 10.1038/sj.emboj.7601845. Epub 2007 Sep 20.


The dynamic modification of nuclear and cytoplasmic proteins with O-linked beta-N-acetylglucosamine (O-GlcNAc) by the O-linked N-acetylglucosaminyltransferase (OGT) is a regulatory post-translational modification that is responsive to various stimuli. Here, we demonstrate that OGT is a central factor for T- and B-lymphocytes activation. SiRNA-mediated knockdown of OGT in T cells leads to an impaired activation of the transcription factors NFAT and NFkappaB. This results in a reduction of IL-2 production consistent with prevention of T-cell activation. OGT is also required for the early activation of B cells mediated by stimulation of the B-cell receptor. Mechanistically, we demonstrate that NFkappaB as well as NFAT are glycosylated with O-GlcNAc after direct binding to OGT. Moreover, kinetic experiments show that O-GlcNAc modification prominently increased shortly after activation of lymphoid cells and it might be required for nuclear translocation of the transcription factors NFkappaB and NFAT.

MeSH terms

  • Alternative Splicing
  • Antigens, CD / biosynthesis
  • Antigens, Differentiation, T-Lymphocyte / biosynthesis
  • B-Lymphocytes / metabolism
  • Glycosylation
  • Humans
  • Interleukin-2 / metabolism
  • Lectins, C-Type
  • Lymphocyte Activation*
  • Lymphocytes / metabolism*
  • Models, Biological
  • N-Acetylglucosaminyltransferases / chemistry
  • N-Acetylglucosaminyltransferases / physiology*
  • NF-kappa B / metabolism
  • NFATC Transcription Factors / metabolism
  • Protein Processing, Post-Translational
  • RNA, Small Interfering / metabolism
  • T-Lymphocytes / metabolism


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Interleukin-2
  • Lectins, C-Type
  • NF-kappa B
  • NFATC Transcription Factors
  • NFATC2 protein, human
  • RNA, Small Interfering
  • N-Acetylglucosaminyltransferases
  • N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase