TY - JOUR
T1 - Profiling of Protein O-GlcNAcylation in Murine CD8+ Effector- and Memory-like T Cells
AU - Lopez Aguilar, Aime
AU - Gao, Yu
AU - Hou, Xiaomeng
AU - Lauvau, Gregoire
AU - Yates, John R.
AU - Wu, Peng
N1 - Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/12/15
Y1 - 2017/12/15
N2 - During an acute infection, antigenic stimulation leads to activation, expansion, and differentiation of naïve CD8+ T cells, first into cytotoxic effector cells and eventually into long-lived memory cells. T cell antigen receptors (TCRs) detect antigens on antigen-presenting cells (APCs) in the form of antigenic peptides bound to major histocompatibility complex I (MHC-I)-encoded molecules and initiate TCR signal transduction network. This process is mediated by phosphorylation of many intracellular signaling proteins. Protein O-GlcNAc modification is another post-translational modification involved in this process, which often has either reciprocal or synergistic roles with phosphorylation. In this study, using a chemoenzymatic glycan labeling technique and proteomics analysis, we compared protein O-GlcNAcylation of murine effector and memory-like CD8+ T cells differentiated in vitro. By quantitative proteomics analysis, we identified 445 proteins that are significantly regulated in either effector- or memory-like T cell subsets. Furthermore, qualitative and quantitative analysis identified highly regulated protein clusters that suggest involvement of this post-translational modification in specific cellular processes. In effector-like T cells, protein O-GlcNAcylation is heavily involved in transcriptional and translational processes that drive fast effector T cells proliferation. During the formation of memory-like T cells, protein O-GlcNAcylation is involved in a more specific, perhaps more targeted regulation of transcription, mRNA processing, and translation. Significantly, O-GlcNAc plays a critical role as part of the "histone code" in both CD8+ T cells subgroups.
AB - During an acute infection, antigenic stimulation leads to activation, expansion, and differentiation of naïve CD8+ T cells, first into cytotoxic effector cells and eventually into long-lived memory cells. T cell antigen receptors (TCRs) detect antigens on antigen-presenting cells (APCs) in the form of antigenic peptides bound to major histocompatibility complex I (MHC-I)-encoded molecules and initiate TCR signal transduction network. This process is mediated by phosphorylation of many intracellular signaling proteins. Protein O-GlcNAc modification is another post-translational modification involved in this process, which often has either reciprocal or synergistic roles with phosphorylation. In this study, using a chemoenzymatic glycan labeling technique and proteomics analysis, we compared protein O-GlcNAcylation of murine effector and memory-like CD8+ T cells differentiated in vitro. By quantitative proteomics analysis, we identified 445 proteins that are significantly regulated in either effector- or memory-like T cell subsets. Furthermore, qualitative and quantitative analysis identified highly regulated protein clusters that suggest involvement of this post-translational modification in specific cellular processes. In effector-like T cells, protein O-GlcNAcylation is heavily involved in transcriptional and translational processes that drive fast effector T cells proliferation. During the formation of memory-like T cells, protein O-GlcNAcylation is involved in a more specific, perhaps more targeted regulation of transcription, mRNA processing, and translation. Significantly, O-GlcNAc plays a critical role as part of the "histone code" in both CD8+ T cells subgroups.
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U2 - 10.1021/acschembio.7b00869
DO - 10.1021/acschembio.7b00869
M3 - Article
C2 - 29125738
AN - SCOPUS:85038587023
SN - 1554-8929
VL - 12
SP - 3031
EP - 3038
JO - ACS Chemical Biology
JF - ACS Chemical Biology
IS - 12
ER -