Disease relevance of HSAJ2425

• Expression of the p65 gene in patients with colorectal cancer: comparison with some histological typing, grading and clinical staging [1].
• For 19 of them expression of examined gene was observed both in cancer and corresponding healthy mucosa. p65 Gene expression was associated with more advanced tumours (T3, T4; p=0.0003) with metastases to lymph nodes (N1, N2; p=0.0003) and distant metastases (p=0.0005) [1].
• Cloning of an NF-kappa B subunit which stimulates HIV transcription in synergy with p65 [2].
• Human intestinal epithelial cell inflammatory responses to amebic infection were inhibited by the intraluminal administration of an antisense oligonucleotide to the human p65 subunit of nuclear factor kappaB, and the role of neutrophils in tissue damage observed with amebiasis was studied by depleting neutrophils from SCID-HU-INT mice [3].
• Overexpression of manganese superoxide dismutase (Mn-SOD) in human breast cancer MCF-7 cells completely abolished TNF-mediated NF-kappaB activation, IkappaB alpha degradation, p65 nuclear translocation, and NF-kappaB-dependent reporter gene expression [4].

Psychiatry related information on HSAJ2425

• In the present study we have examined NF-kB immunoreactivity, by means of NF-kB p65 immunohistochemistry, in the brains of seven patients with Alzheimer's disease, two patients with Creutzfeldt-Jakob disease associated with PrP amyloid deposition, and seven age-matched controls [5].

High impact information on HSAJ2425

• The transcription factor NF-kappa B is a heterodimer consisting of two proteins encoded by different members of the rel gene family (p50 and p65) [6].
• Expression of the p65 delta cDNA in Rat-1 fibroblasts resulted in focus formation, anchorage-independent growth in soft agar, and tumor formation in athymic nude mice, effects not obtained with expression of p65 or a p65 delta mutant that contains a disruption within the transcriptional activation domain [7].
• Secretory leucoprotease inhibitor binds to NF-kappaB binding sites in monocytes and inhibits p65 binding [8].
• Using a functional assay that measures the surface deposition of C3 activated via the classical complement pathway, we show that Crry/p65-expressing cells have a markedly decreased amount of C3 deposited on them as compared with control cells expressing the antisense construct or cells expressing MCR1 or MCR2 [9].
• In electrophoretic mobility shift assays and upon sedimentation through glycerol gradients, NF-kappa B appears to exist as a heterodimer composed of one p50 and one p65 subunit whereas data from gel filtration suggest a higher order complex [10].

Chemical compound and disease context of HSAJ2425

• Muscarinic receptor-mediated NF-kappaB activation was confirmed by observing the translocation of the active subunit (p65) of NF-kappaB to the nucleus by the muscarinic agonist, oxotremorine M (oxoM), in SH-SY5Y neuroblastoma cells expressing muscarinic receptors that are predominantly of the M3 subtype [11].
• Overexpression of p65/RelA potentiates curcumin-induced apoptosis in HCT116 human colon cancer cells [12].
• Decreased expression of T-cell NF-kappaB p65 subunit in steroid-resistant nephrotic syndrome [13].
• Ciglitazone induces early cellular proliferation and NF-kappaB transcriptional activity in colon cancer cells through p65 phosphorylation [14].
• Hypoxic endothelia showed a > 10-fold increase in sensitivity to inhibitors of proteasome activation, and combinations of hypoxia and LPS enhanced proteasome-dependent cytoplasmic-to-nuclear localization of the nuclear transcription factor-kappa B p65 (Rel A) subunit [15].

Biological context of HSAJ2425

• We have now identified the p65 gene as a novel member of the superfamily of genes that encode nuclear receptors for various hydrophobic ligands such as steroids, vitamin D, retinoic acid, and thyroid hormones. these receptors are composed of several domains important in hormone binding, DNA binding, dimerization, and transcription activation [16].
• We did not find association between the age, gender, tumour localization, histological type and p65 gene expression [1].
• In addition, we have identified in the cloned p65 cDNA fragment sequences encoding two peptides, obtained by CNBr cleavage, whose amino acid sequences were previously established [16].
• Similar results were obtained for the reciprocal transrepression of a GC receptor (GR) element-driven reporter gene by p65 [17].
• Antisera raised against two mitosis-specific protein kinases from human cells recognized a single 65-kDa polypeptide (p65) that is present in similar amounts in interphase and mitotic cell extracts [18].

Anatomical context of HSAJ2425

• The oncofetal protein p65: a new member of the steroid/thyroid receptor superfamily [16].
• We now provide direct biochemical evidence for the presence of an endogenous pool of inducible p65 homodimers in intact human T cells [19].
• In both the primary tumor cells from our patient and PEL cell lines, AZT selectively blocked nuclear entry of the NF-kappaB heterodimer p50 and p65, an effect not seen with other nonthymidine antiviral nucleosides [20].
• We have purified this activity from the HeLa cell cytosol and have shown that it represents a performed heteromeric complex between p65 (RelA) and c-Rel [21].
• In Bcl-3-transduced and IL-10-pretreated macrophages, LPS-induced nuclear translocation of nuclear factor kappaB (NF-kappaB) p65 was not impaired [22].

Associations of HSAJ2425 with chemical compounds

• A reduction in the expression of p65 was produced by treatment with the phosphorothioate antisense oligodeoxynucleotide [23].
• Site-directed mutagenesis studies indicate that the homodimerization function of p65 is dependent upon the presence of cysteine 216 and a conserved recognition motif for protein kinase A (RRPS; amino acids 273 to 276), both of which reside within a 91-amino-acid segment of the Rel homology domain that mediates self-association [19].
• Using the methylene blue-mediated cross-linking method (Z. R. Liu, A. M. Wilkie, M. J. Clemens, and C. W. Smith, RNA 2:611-621, 1996), a 65-kDa protein (p65) was shown to interact with the U1-5'ss duplex during spliceosome assembly (Z. R. Liu, B. Sargueil, and C. W. Smith, Mol. Cell. Biol. 18:6910-6920, 1998) [24].
• Furthermore, the p65 antisense oligomer effectively abolished an upregulation of CD11b that was produced by formyl-met-leu-phe and TPA [23].
• Cotransfection of NFkappaB p50 and p65 cDNA induced 5-FU resistance in MCF-7 cells [25].

Regulatory relationships of HSAJ2425

• Alcohol inhibited IL-2-induced NF-kappaB p65 protein expression and calcium mobilization by NK cells [26].

Other interactions of HSAJ2425

• The immunoreactive NF kappa B and I kappa B were localized in the tissues. p65 protein was found in the nucleus and cytoplasm of cells in the amnion, chorion laeve and decidua [27].
• Unlike human DAF, however, no phosphatidylinositol-specific phospholipase C-sensitive Crry/p65 protein form can be demonstrated on lymphocytes or erythrocytes [28].
• However, the combined stimulation did not result in enhanced p50 and p65 protein expression [29].
• We determined the production of prostaglandin (PG) E2 and D2 in colon mucosa, as well as cyclooxygenase (COX)-1 and -2 and nuclear transcription factor NF-kappa B (NF-kappaB) p65 protein expression [30].
• Resveratrol did not modify PGD2 levels but returned the decreased PGE2 values to basal levels and also reduced COX-2 and the NF-kappaB p65 protein expression [30].

Analytical, diagnostic and therapeutic context of HSAJ2425

• In electrophoretic mobility shift assays and upon UV cross-linking to DNA, gel-purified p65 is shown to be a kappa B-specific DNA-binding protein on its own [10].
• A combination of promoter deletion and mutational analyses, chromatin immunoprecipitation assays, and co-immunoprecipitation studies indicates that p65 and histone deacetylases 4 cooperate to inhibit the ability of MEF2 factors to induce the KLF2 promoter [31].
• Our confocal microscopy study clearly showed that DIM blocks the translocation of p65, a subunit of NF-kappaB to the nucleus [32].
• These results were also supported, for the first time, by animal experiments, p65 cDNA transfection and p65 small interfering RNA studies, which clearly showed that a specific target (NF-kappaB) was affected in vivo [33].
• The phosphorylation of p65 by CaMKIV resulted in recruitment of transcription coactivator cAMP-response element-binding protein-binding protein and concomitant release of corepressor silencing mediator for retinoid and thyroid hormone receptors, as demonstrated by the glutathione S-transferase pull down and mammalian two hybrid assays [34].

References