Requirement for O‐linked N‐acetylglucosaminyltransferase in lymphocytes activation

The dynamic modification of nuclear and cytoplasmic proteins with O‐linked β‐ 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 NFκB. 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 NFκB 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 NFκB and NFAT.