Disease relevance of Nupr1

• p8 is a transcription cofactor whose expression is strongly and rapidly activated in pancreatic acinar cells during the acute phase of pancreatitis [1].
• Together, these data suggest that maintenance of the transformed phenotype of pituitary GH3 cells requires expression of p8 and that it may play a similar role when reexpressed in a subset of lactotropes that form prolactinomas in vivo [2].
• One of these, p8 (candidate of metastasis-1), encodes a native high-mobility group-like transcription factor previously shown to be necessary for ras-mediated transformation of mouse embryonic fibroblasts and also implicated in breast cancer progression [2].
• Thus, p8 is an excellent candidate as a novel biomarker of demyelination [3].
• Enhanced expression of p8 is also observed in the spinal cords of mice with acute experimental autoimmune encephalomyelitis (EAE) induced by PLP139-151 peptide (10x) [3].

High impact information on Nupr1

• The Orphan Nuclear Receptor RORgammat Directs the Differentiation Program of Proinflammatory IL-17(+) T Helper Cells [4].
• CONCLUSIONS: Nuclear factor of activated T cells plays a critical role in the regulation of bowel inflammation by nonlymphoid immune cells, and B cells suppress bowel inflammation by innate immune cells [5].
• RESULTS: Nuclear factor of activated T cells c2-deficient, recombinase activating gene-deficient animals spontaneously developed a severe inflammatory bowel syndrome that resembled ulcerative colitis but was composed entirely of nonlymphocytes [5].
• Abnormal spermatogenesis and reduced fertility in transition nuclear protein 1-deficient mice [6].
• Studies conducted with MiaPaCa2 and Panc1 cell lines showed that cannabinoid administration (a) induced apoptosis, (b) increased ceramide levels, and (c) up-regulated mRNA levels of the stress protein p8 [7].

Chemical compound and disease context of Nupr1

• Reexpression of p8 contributes to tumorigenic properties of pituitary cells and appears in a subset of prolactinomas in transgenic mice that hypersecrete luteinizing hormone [2].
• In an Affymetrix GeneChip analysis, the stress-associated gene p8 was strongly upregulated (>10x) during cuprizone-induced demyelination but not remyelination [3].
• 2,3,7,8-Tetrachlorodibenzo-p-dioxin receptors in wild type and variant mouse hepatoma cells. Nuclear location and strength of nuclear binding [8].
• Suppression of Staphylococcal Enterotoxin B-induced Toxicity by a Nuclear Import Inhibitor [9].
• Tests which showed good correlation with bioassay results and thus were considered good predictors of tumorigenic potential were: Sustained Epidermal Hyperplasia as measured by epidermal thickness, Nuclear Area of epidermal basal cells, Modified Ames Test and DMSO extraction for PAC content [10].

Biological context of Nupr1

• Taken together, our data indicate that p8 is a stage-specific component of the gonadotrope transcriptome that may play a functional role in the initiation of LH beta gene expression during embryonic cellular differentiation [11].
• Orphan Nuclear Receptor Small Heterodimer Partner Inhibits Transforming Growth Factor-beta Signaling by Repressing SMAD3 Transactivation [12].
• p8-deficient fibroblasts grow more rapidly and are more resistant to adriamycin-induced apoptosis [13].
• We also report that p8 mRNA expression is strongly activated in fibroblasts after cell growth arrest induced by serum deprivation or confluence [13].
• In conclusion, p8 is a cell growth inhibitor that facilitates apoptosis induced in fibroblasts by DNA damage [13].

Anatomical context of Nupr1

• In addition, expression of p8 mRNA in developing mouse pituitary glands mirrored its expression in the gonadotrope-derived cell lines and coincided with the first detectable appearance of LH beta mRNA [11].
• In contrast, p8 mRNA was undetectable in the pituitary glands of normal adults [11].
• Compared with wild-type controls, the death of oligodendrocytes in p8-/- mice is delayed, as is microglial recruitment to areas of demyelination [3].
• Promoter regions involved in the regulation of p8 gene expression in NIH 3T3 cells were analysed [14].
• The corpus callosum of p8-/- mice demyelinates at a slower rate than wild-type mice, suggesting that p8 exacerbates CNS inflammation and demyelination [3].

Associations of Nupr1 with chemical compounds

• We also localized the cellular source of p8 during cuprizone treatment, and further found elevated expression during embryogenesis but not in normal adult brain [3].
• Inactivation of stress protein p8 increases murine carbon tetrachloride hepatotoxicity via preserved CYP2E1 activity [15].
• The Role of X/Y Linker Region and N-terminal EF-hand Domain in Nuclear Translocation and Ca2+ Oscillation-inducing Activities of Phospholipase C{zeta}, a Mammalian Egg-activating Factor [16].
• Furthermore, during the course of the cooling process to 15 degrees C, the increased expression of desaturase mRNA became evident at 27 degrees C. Nuclear run-on analysis and actinomycin D chase experiments revealed that the elevation of the mRNA level was due to increases in both transcription and mRNA stability [17].
• The Orphan Nuclear Receptor, NOR-1, Is a Target of {beta}-Adrenergic Signaling in Skeletal Muscle [18].

Physical interactions of Nupr1

• Embryonic expression of the luteinizing hormone beta gene appears to be coupled to the transient appearance of p8, a high mobility group-related transcription factor [11].

Other interactions of Nupr1

• p8 improves pancreatic response to acute pancreatitis by enhancing the expression of the anti-inflammatory protein pancreatitis-associated protein I [1].
• Finally, demonstration that p53 is a negative trans-activator of p8 suggests the presence of a complex autoregulatory loop [13].
• Rat p8 mRNA was discovered because of its strong activation in pancreas during the acute phase of pancreatitis [14].
• BACKGROUND/AIMS: Nuclear factor kappa B (NF-kappa B) is a primary regulator of gene expression and is activated during hepatic ischemia/reperfusion injury [19].
• (ii) Nuclear localization of Nrf2 coincides with increased DNA binding of a putative Nrf2/MafK heterodimer to its cognate cis-regulatory site, i.e., the antioxidant-responsive element (ARE) [20].

Analytical, diagnostic and therapeutic context of Nupr1

• We verified this upregulation (>15x) of p8 in the CNS during demyelination by real-time polymerase chain reaction (PCR) [3].
• Dexamethasone suppresses expression of Nuclear Factor-kappaB in the cells of tracheobronchial lavage fluid in premature neonates with respiratory distress [21].
• RESULTS: Nuclear transplantation was successful in 89.8-94.4% of GV-ooplast complexes, and maturation rate of the reconstructed oocytes was 93.5-97.9% [22].
• Exp Dermatology 2007; 16: 94-97.Abstract: Nuclear receptor binding of 1,25(OH)(2)-vitamin D(3) (vitamin D) in skin keratinocytes of epidermis, hair sheaths and sebaceous glands was discovered through receptor microscopic autoradiography [23].
• Animal models are currently used to verify the biodistribution of different radiopharmaceuticals before its clinical application in Nuclear Medicine; however, there may be some limitations [24].

References