ENA0000GenomicsMultiomicsNeuroscience and Physiology, SUNY Upstate Medical Univhttps://www.ebi.ac.uk/ena/browser/view/PRJNA110359Homo sapiensCD3-positive T cells were negatively isolated from 10 SLE patients and 9 healthy controls without SLE. All of the SLE samples and control samples were compared with one another to identify baseline differences in expression due to the disease. Next, T cell preparations from 4 of the control subjects were stimulated with either Nitric Oxide (NOC-18) 600 uM for 24hr or stimulated through CD3/CD28 for 24hr to determine which genes were responsive to these signaling mechanisms. Here, we show that activity of the mammalian target of rapamycin (mTOR), which is a sensor of the mitochondrial transmembrane potential, is increased in SLE T cells. Activation of mTOR was inducible by NO, a key trigger of MHP which in turn enhanced the expression of HRES-1/Rab4, a small GTPase that regulates recycling of surface receptors through early endosomes. Expression of HRES-1/Rab4 was increased in SLE T cells and, in accordance with its dominant impact on the endocytic recycling of CD4, it was inversely correlated with diminished CD4 expression. HRES-1/Rab4 over-expression was also inversely correlated with diminished TCRζ protein levels. Combined with follow up studies, these results suggest that activation of mTOR causes the loss of TCRζ in lupus T cells through HRES-1/Rab4-dependent lysosomal degradation. Overall design: 10 replicate T cell samples from SLE (Lupus) patients 9 replicate T cell samples from healthy control (BC) subjects 4 replicate Nitric Oxide (NOC-18) stimulated T cell samples from 4 of the control subjects 4 replicate CD3/CD28 stimulated T cell samples from 4 of the control subjectsENAmulticellular organismal catabolic process, single-organism catabolic process, Mechanistic target of rapamycin, lupus erythematosus, dTAF[[II]]230, TAF[[II]]250, d230, 2610315D21Rik, RAB4, degradation, FKBP12-rapamycin complex-associated protein, CG5092, TAF200, l(3)84Ab, dTAFII250, FRAP1, FRAP2, BG:DS00004.13, mTOR, l(2)k03905, FRAP/TOR, TAFII-250, TAF250/230, HRES-1|RAB4, DmelCG5092, EfW1, l(2)k17004, Cell, DmTOR, dTAF230, dmTAF[[II]]230, 2.7.11.1, TAFII250, dmTAF1, Taf230, p230, TAF[[II]]250/230, TFIID, RAFT1, TOR, Mammalian target of rapamycin, activation, RAPT1, DmelCG8274, TAF250, Taf[[II]]250, Taf200, dTAF[[II]]250, TAF[[II]]230, breakdown, Bx34, TFIID TAF250, cel, cell, lupus, Rapamycin and FKBP12 target 1, CT24745, Rapamycin target protein 1, Taf1p, AI327068, flat, tor, TAF[II]250, catabolism., Tpr, TPR, FRAP, CG17603, TAF[[II]], dtor, HRES-1, loss of, dTAF250, HRES1, DmelCG17603, CT16317, Taf250, HRES-1/RAB4, SR3-5, CG8274, 5092, MTOR, TAF, Frap1, CT24817, dTOR, dTor, TAF230, FK506-binding protein 12-rapamycin complex-associated protein 1, TAF1human being, human., man0.00.00.00.00.00falseHomo sapiensActivation of mTOR controls the loss of TCRζ in lupus T cells through HRES-1/Rab4-regulated lysosomal degradation2022-05-122014-02-11PRJNA110359GSE13887192018599606