Article
- The EMBO Journal (2007) 26, 4368 - 4379
- doi:10.1038/sj.emboj.7601845
Published online: 20 September 2007
Subject Categories:
Requirement for O-linked N-acetylglucosaminyltransferase in lymphocytes activation
Alexander Golks, Thi-Thanh Thao Tran, Jean Francois Goetschy and Danilo Guerini
- Autoimmunity and Transplantation, Novartis Pharma AG, Basel, Switzerland
Correspondence to:
Danilo Guerini, Autoimmunity and Transplantation, Novartis Pharma AG, Forum 1, Novartis Campus, Basel CH-4056, Switzerland. Tel.: +41 61 3243862; Fax: +41 61 3242488; E-mail: danilo.guerini@novartis.com
Received 15 March 2007; Accepted 10 August 2007
Abstract
The dynamic modification of nuclear and cytoplasmic proteins with O-linked 
-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 NF
B. 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 NFB 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 NFB and NFAT.
Keywords:
- lymphocytes activation,
- OGT,
- O-GlcNAc
