Requirement for O-linked N-acetylglucosaminyltransferase in lymphocytes activation.

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, Antigens, Differentiation, T-Lymphocyte, B-Lymphocytes, Glycosylation, Humans, Interleukin-2, Lectins, C-Type, Lymphocyte Activation, Lymphocytes, Models, Biological, N-Acetylglucosaminyltransferases, NF-kappa B, NFATC Transcription Factors, Protein Processing, Post-Translational, RNA, Small Interfering, T-Lymphocytes
EMBO J.
Date: Oct. 17, 2007
Download Curated Data For This Publication
149097
Switch View:
  • Interactions 6