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Article
Subject Categories: Signal Transduction | Immunology
The EMBO Journal (2007) 26, 4368–4379, doi:10.1038/sj.emboj.7601845
Published online 20 September 2007
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

To whom correspondence should be addressed
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; Published online 20 September 2007.
Abstract
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.
Keywords: lymphocytes activation, OGT, O-GlcNAc
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