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Publication : SNX27 links DGKζ to the control of transcriptional and metabolic programs in T lymphocytes.

First Author  Tello-Lafoz M Year  2017
Journal  Sci Rep Volume  7
Issue  1 Pages  16361
PubMed ID  29180720 Mgi Jnum  J:255770
Mgi Id  MGI:6110196 Doi  10.1038/s41598-017-16370-w
Citation  Tello-Lafoz M, et al. (2017) SNX27 links DGKzeta to the control of transcriptional and metabolic programs in T lymphocytes. Sci Rep 7(1):16361
abstractText  Sorting nexin 27 (SNX27) recycles PSD-95, Dlg1, ZO-1 (PDZ) domain-interacting membrane proteins and is essential to sustain adequate brain functions. Here we define a fundamental SNX27 function in T lymphocytes controlling antigen-induced transcriptional activation and metabolic reprogramming. SNX27 limits the activation of diacylglycerol (DAG)-based signals through its high affinity PDZ-interacting cargo DAG kinase zeta (DGKzeta). SNX27 silencing in human T cells enhanced T cell receptor (TCR)-stimulated activator protein 1 (AP-1)- and nuclear factor kappaB (NF-kappaB)-mediated transcription. Transcription did not increase upon DGKzeta silencing, suggesting that DGKzeta function is dependent on SNX27. The enhanced transcriptional activation in SNX27-silenced cells contrasted with defective activation of the mammalian target of rapamycin (mTOR) pathway. The analysis of Snx27 (-/-) mice supported a role for SNX27 in the control of T cell growth. This study broadens our understanding of SNX27 as an integrator of lipid-based signals with the control of transcription and metabolic pathways.
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