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Requirement for O‐linked N ‐acetylglucosaminyltransferase in lymphocytes activation
Author(s) -
Golks Alexander,
Tran ThiThanh Thao,
Goetschy Jean Francois,
Guerini Danilo
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601845
Subject(s) - biology , genetics , microbiology and biotechnology
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.