XBP1, X-box binding protein 1; Hsp72, heat shock 70 kDa protein 1; qPCR, quantitative real-time polymerase chain reaction; ANOVA, analysis of variance; HSD, honestly significant difference; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; RT-PCR, Reverse transcription polymerase chain reaction; usXBP1, un-spliced XBP1; sXBP1, spliced XBP1.
XBP1, X-box binding protein 1; ERSE, endoplasmic reticulum-stress response element; BiP, binding immunoglobulin protein; GRP94, heat shock protein 90 kDa beta member 1; Herpud1, homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein; UPRE, UPR element; ANOVA, analysis of variance; qPCR, quantitative real-time polymerase chain reaction; HRD1, E3 ubiquitin-protein ligase synoviolin; EDEM1, endoplasmic reticulum degradation enhancing alpha-mannosidase-like protein 1; SLC25A1, solute carrier family 25 member 1.
The research by UT Southwestern Medical Center potentially shows that the spliced X-box binding protein 1
(Xbp1s), appears to influence the body's sensitivity to insulin and leptin signaling.
X-box binding protein 1 (XBP1) is the transcription factor activated by IRE1 during ER stress.
Zhang, "Preconditioning with endoplasmic reticulum stress mitigates retinal endothelial inflammation via activation of X-box binding protein 1," The Journal of Biological Chemistry, vol.
"We show that p38 mitogen-activated protein kinase (p38 MAPK) phosphorylates the spliced form of X-box binding protein 1
(Xbp1s) on its Thr48 and Ser61 residues and greatly enhances its nuclear migration in mice, whereas mutation of either residue to alanine substantially reduces its nuclear translocation and activity.
When the predicted TF genes were matched to the DEGs, we found that the genes CCAAT/enhancer binding protein gamma, fli-1 proto-oncogene, ETS transcription factor (FLI1), hes family bHLH transcription factor 1 (HES1), interferon regulatory factor 1 (IRF1), junB proto-oncogene (JUNB), signal transducer and activator of transcription 4, and X-box binding protein 1
were upregulated, and forkhead box protein P3 (FOXP3), homeobox D8 (HOXD8), and peroxisome proliferator activated receptor gamma (PPARG) were downregulated (Figure 2, Table 2).
The researchers have now shown that a transcription factor that normally helps relieve ER stress, called X-box binding protein 1
(XBP-1), is unable to function in obese mice.