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Gene Review

HSAJ2425  -  p65 protein

Homo sapiens

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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


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


Other interactions of HSAJ2425


Analytical, diagnostic and therapeutic context of HSAJ2425


  1. Expression of the p65 gene in patients with colorectal cancer: comparison with some histological typing, grading and clinical staging. Balcerczak, M., Balcerczak, E., Pasz-Walczak, G., Kordek, R., Mirowski, M. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. (2004) [Pubmed]
  2. Cloning of an NF-kappa B subunit which stimulates HIV transcription in synergy with p65. Schmid, R.M., Perkins, N.D., Duckett, C.S., Andrews, P.C., Nabel, G.J. Nature (1991) [Pubmed]
  3. Epithelial cell-initiated inflammation plays a crucial role in early tissue damage in amebic infection of human intestine. Seydel, K.B., Li, E., Zhang, Z., Stanley, S.L. Gastroenterology (1998) [Pubmed]
  4. Overexpression of manganese superoxide dismutase suppresses tumor necrosis factor-induced apoptosis and activation of nuclear transcription factor-kappaB and activated protein-1. Manna, S.K., Zhang, H.J., Yan, T., Oberley, L.W., Aggarwal, B.B. J. Biol. Chem. (1998) [Pubmed]
  5. NF-kB immunoreactivity is observed in association with beta A4 diffuse plaques in patients with Alzheimer's disease. Ferrer, I., Martí, E., López, E., Tortosa, A. Neuropathol. Appl. Neurobiol. (1998) [Pubmed]
  6. Generation of p50 subunit of NF-kappa B by processing of p105 through an ATP-dependent pathway. Fan, C.M., Maniatis, T. Nature (1991) [Pubmed]
  7. Identification of a naturally occurring transforming variant of the p65 subunit of NF-kappa B. Narayanan, R., Klement, J.F., Ruben, S.M., Higgins, K.A., Rosen, C.A. Science (1992) [Pubmed]
  8. Secretory leucoprotease inhibitor binds to NF-kappaB binding sites in monocytes and inhibits p65 binding. Taggart, C.C., Cryan, S.A., Weldon, S., Gibbons, A., Greene, C.M., Kelly, E., Low, T.B., O'neill, S.J., McElvaney, N.G. J. Exp. Med. (2005) [Pubmed]
  9. Distinct receptor and regulatory properties of recombinant mouse complement receptor 1 (CR1) and Crry, the two genetic homologues of human CR1. Molina, H., Wong, W., Kinoshita, T., Brenner, C., Foley, S., Holers, V.M. J. Exp. Med. (1992) [Pubmed]
  10. NF-kappa B contacts DNA by a heterodimer of the p50 and p65 subunit. Urban, M.B., Schreck, R., Baeuerle, P.A. EMBO J. (1991) [Pubmed]
  11. Nuclear Factor-{kappa}B Activated by Capacitative Ca2+ Entry Enhances Muscarinic Receptor-mediated Soluble Amyloid Precursor Protein (sAPP{alpha}) Release in SH-SY5Y Cells. Choi, S., Kim, J.H., Roh, E.J., Ko, M.J., Jung, J.E., Kim, H.J. J. Biol. Chem. (2006) [Pubmed]
  12. Overexpression of p65/RelA potentiates curcumin-induced apoptosis in HCT116 human colon cancer cells. Collett, G.P., Campbell, F.C. Carcinogenesis (2006) [Pubmed]
  13. Decreased expression of T-cell NF-kappaB p65 subunit in steroid-resistant nephrotic syndrome. Aviles, D.H., Matti Vehaskari, V., Manning, J., Ochoa, A.C., Zea, A.H. Kidney Int. (2004) [Pubmed]
  14. Ciglitazone induces early cellular proliferation and NF-kappaB transcriptional activity in colon cancer cells through p65 phosphorylation. Chen, F., Harrison, L.E. Int. J. Biochem. Cell Biol. (2005) [Pubmed]
  15. Hypoxia enhances induction of endothelial ICAM-1: role for metabolic acidosis and proteasomes. Zünd, G., Uezono, S., Stahl, G.L., Dzus, A.L., McGowan, F.X., Hickey, P.R., Colgan, S.P. Am. J. Physiol. (1997) [Pubmed]
  16. The oncofetal protein p65: a new member of the steroid/thyroid receptor superfamily. Hanausek, M., Szemraj, J., Adams, A.K., Walaszek, Z. Cancer Detect. Prev. (1996) [Pubmed]
  17. Glucocorticoids repress NF-kappaB-driven genes by disturbing the interaction of p65 with the basal transcription machinery, irrespective of coactivator levels in the cell. De Bosscher, K., Vanden Berghe, W., Vermeulen, L., Plaisance, S., Boone, E., Haegeman, G. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  18. Identification of mitosis-specific p65 dimer as a component of human M phase-promoting factor. Meikrantz, W., Suprynowicz, F.A., Halleck, M.S., Schlegel, R.A. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  19. A novel NF-kappa B complex containing p65 homodimers: implications for transcriptional control at the level of subunit dimerization. Ganchi, P.A., Sun, S.C., Greene, W.C., Ballard, D.W. Mol. Cell. Biol. (1993) [Pubmed]
  20. Potentiation of TRAIL-induced apoptosis in primary effusion lymphoma through azidothymidine-mediated inhibition of NF-kappa B. Ghosh, S.K., Wood, C., Boise, L.H., Mian, A.M., Deyev, V.V., Feuer, G., Toomey, N.L., Shank, N.C., Cabral, L., Barber, G.N., Harrington, W.J. Blood (2003) [Pubmed]
  21. Purification, reconstitution, and I kappa B association of the c-Rel-p65 (RelA) complex, a strong activator of transcription. Hansen, S.K., Baeuerle, P.A., Blasi, F. Mol. Cell. Biol. (1994) [Pubmed]
  22. IL-10-inducible Bcl-3 negatively regulates LPS-induced TNF-alpha production in macrophages. Kuwata, H., Watanabe, Y., Miyoshi, H., Yamamoto, M., Kaisho, T., Takeda, K., Akira, S. Blood (2003) [Pubmed]
  23. Antisense oligonucleotides to the p65 subunit of NF-kappa B block CD11b expression and alter adhesion properties of differentiated HL-60 granulocytes. Sokoloski, J.A., Sartorelli, A.C., Rosen, C.A., Narayanan, R. Blood (1993) [Pubmed]
  24. p68 RNA helicase is an essential human splicing factor that acts at the U1 snRNA-5' splice site duplex. Liu, Z.R. Mol. Cell. Biol. (2002) [Pubmed]
  25. Mechanistic and predictive profiling of 5-Fluorouracil resistance in human cancer cells. Wang, W., Cassidy, J., O'Brien, V., Ryan, K.M., Collie-Duguid, E. Cancer Res. (2004) [Pubmed]
  26. Alcohol suppresses IL-2-induced CC chemokine production by natural killer cells. Zhang, T., Guo, C.J., Douglas, S.D., Metzger, D.S., O'Brien, C.P., Li, Y., Wang, Y.J., Wang, X., Ho, W.Z. Alcohol. Clin. Exp. Res. (2005) [Pubmed]
  27. Localization of nuclear factor-kappa B (NF kappa B) and inhibitory factor-kappa B (I kappa B) in human fetal membranes and decidua at term and preterm delivery. Yan, X., Sun, M., Gibb, W. Placenta (2002) [Pubmed]
  28. Mouse Crry/p65. Characterization of monoclonal antibodies and the tissue distribution of a functional homologue of human MCP and DAF. Li, B., Sallee, C., Dehoff, M., Foley, S., Molina, H., Holers, V.M. J. Immunol. (1993) [Pubmed]
  29. Interferon-gamma modulates the lipopolysaccharide-induced expression of AP-1 and NF-kappa B at the mRNA and protein level in human monocytes. de Wit, H., Hoogstraten, D., Halie, R.M., Vellenga, E. Exp. Hematol. (1996) [Pubmed]
  30. The effects of resveratrol, a phytoalexin derived from red wines, on chronic inflammation induced in an experimentally induced colitis model. Martín, A.R., Villegas, I., Sánchez-Hidalgo, M., de la Lastra, C.A. Br. J. Pharmacol. (2006) [Pubmed]
  31. Tumor necrosis factor alpha-mediated reduction of KLF2 is due to inhibition of MEF2 by NF-kappaB and histone deacetylases. Kumar, A., Lin, Z., SenBanerjee, S., Jain, M.K. Mol. Cell. Biol. (2005) [Pubmed]
  32. Inhibition of nuclear translocation of nuclear factor-{kappa}B contributes to 3,3'-diindolylmethane-induced apoptosis in breast cancer cells. Rahman, K.W., Sarkar, F.H. Cancer Res. (2005) [Pubmed]
  33. Inactivation of nuclear factor kappaB by soy isoflavone genistein contributes to increased apoptosis induced by chemotherapeutic agents in human cancer cells. Li, Y., Ahmed, F., Ali, S., Philip, P.A., Kucuk, O., Sarkar, F.H. Cancer Res. (2005) [Pubmed]
  34. Ca2+/calmodulin-dependent protein kinase IV stimulates nuclear factor-kappa B transactivation via phosphorylation of the p65 subunit. Jang, M.K., Goo, Y.H., Sohn, Y.C., Kim, Y.S., Lee, S.K., Kang, H., Cheong, J., Lee, J.W. J. Biol. Chem. (2001) [Pubmed]
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