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| Subject Categories: Signal Transduction | Immunology |
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| The EMBO Journal
(2007) 26, 4368–4379, doi:10.1038/sj.emboj.7601845 Published online 20 September 2007 |
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| Requirement for O-linked N-acetylglucosaminyltransferase in lymphocytes activation |
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| Alexander Golks, Thi-Thanh Thao Tran, Jean Francois Goetschy and Danilo Guerini |
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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. |
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| Abstract |
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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. |
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| Keywords: lymphocytes activation, OGT, O-GlcNAc |
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