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Gene Review

p53-ps  -  Wistar clone pR53P1 p53 pseudogene

Rattus norvegicus

 
 
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Disease relevance of p53

 

Psychiatry related information on p53

 

High impact information on p53

  • The p53 protein is rendered temperature-sensitive by a point mutation [6].
  • Remarkably, inhibition of protein synthesis at 37 degrees C also results in the rapid appearance of mutant p53 in the cell nucleus [6].
  • Protein synthesis required to anchor a mutant p53 protein which is temperature-sensitive for nuclear transport [6].
  • Furthermore, p68 is the HSP70 heat shock protein cognate, found in elevated levels in a p53-overproducing cell line [7].
  • p53RDL1 regulates p53-dependent apoptosis [8].
 

Chemical compound and disease context of p53

 

Biological context of p53

  • Cloning and characterization of two processed p53 pseudogenes from the rat genome [13].
  • Although the rat alternatively spliced p53 mRNA has so far not been described, our data suggest that these two processed pseudogenes may have been generated by integration of different mRNA intermediates into germ-line DNA [13].
  • However, how the mitochondrial p53 pathway mediates neuronal apoptosis after cerebral ischemia remains unclear [1].
  • To examine the effect of a specific p53 inhibitor on the mitochondrial p53 pathway and apoptotic cell death after tGCI, we intravenously administered pifithrin-alpha (PFT) [1].
  • CONCLUSIONS: Members of the p-53 signal transduction pathway are significantly involved in glaucoma and ONT [14].
 

Anatomical context of p53

  • Recent studies have shown that the p53 protein can directly induce permeabilization of the outer mitochondrial membrane by forming a inhibitory complex with a protective Bcl-2 family protein, resulting in cytochrome c release [1].
  • DADS increased the protein levels of p53, cytochrome c and phosphated JNK within 24 h of treatment and it decreased the levels of Bcl-2 and those factors may have led to the mitochondria depolarization of N18 cells [15].
  • Reoxygenation of hypoxic cardiac myocytes induced apoptosis in 25-30% of the cells and was also independent of p53 by the same criteria [3].
  • Two molecularly distinct intracellular pathways to oligodendrocyte differentiation: role of a p53 family protein [16].
  • p53/58 is a transmembrane protein that continuously recycles between the ER and pre-Golgi intermediates composed of vesicular-tubular clusters (VTCs) found in the cell periphery and at the cis face of the Golgi complex [17].
 

Associations of p53 with chemical compounds

  • Immunohistochemical study of cell proliferation, Bcl-2, p53, and caspase-3 expression on preneoplastic changes induced by cadmium and zinc chloride in the ventral rat prostate [18].
  • Haloperidol-induced apoptosis is mediated by the sigma2 (sigma2) receptor system and does not involve the expected antagonism of the dopamine D(2) receptor, nor is it influenced by Vitamin E- or p53/Bax-mediated events [19].
  • Dietary folate deprivation progressively decreased, whereas supplementation increased, steady-state levels of p53 transcript over 5 weeks (P<0.05) [20].
  • These results suggest that TH and RA activate the same intracellular pathway leading to oligodendrocyte differentiation, and that this pathway depends on a p53 family protein [16].
  • To determine if ras proteins are themselves modified by a similar type of methylation reaction, we incubated rat embryo fibroblasts transformed with p53 and activated Ha-ras oncogenes with L-[methyl-3H]methionine under conditions in which the isotope was converted to the methyl donor S-adenosyl-L-[methyl-3H]methionine [21].
 

Physical interactions of p53

  • The results suggest that hsp84 binds mutant p53 in a spatial and/or conformation dependent manner [22].
  • Heat shock protein 84 forms a complex with mutant p53 protein predominantly within a cytoplasmic compartment of the cell [22].
 

Regulatory relationships of p53

  • Introduction of p53His175 into Rat-1/myc cells reversed this effect, indicating that Myc-accelerated doxorubicin-induced apoptosis requires functional p53 [23].
 

Other interactions of p53

  • An irregular expression of Bcl2 protein was found in untreated and treated lymphomas, while the expression of protein p53 as well as MDM2 was not observed [24].
  • RNA expression studies, based on a multiplexed-nuclease protection assay, demonstrated that cell cycle- and apoptosis-related genes were differentially expressed within 48 h of POH treatment; p21(Cip1/WAF1), bax, bad, and annexin I were induced; cyclin E and cyclin-dependent kinase 2 were repressed; and bcl-2 and p53 were unchanged [25].
  • These results suggest that Fas receptor may contribute to excitotoxic neuronal death in cooperation with p53, and further implicates the Fas pathway in the pathophysiology of neurodegenerative diseases [26].
  • Northern blot analysis indicated that bcl-2 and c-fos but not p53 and c-myc may participate in mediating H2O2-Fe(II)-induced VSMC apoptosis [27].
  • p53-mediated upregulation of BAX gene transcription is not involved in Bax-alpha protein overexpression in the left ventricle of spontaneously hypertensive rats [11].
 

Analytical, diagnostic and therapeutic context of p53

  • We have cloned, by the polymerase chain reaction (PCR), two rat genomic fragments of 1.3 and 1.2 kb, both of which hybridize to a human p53 cDNA probe [13].
  • Western blot analysis and immunofluorescent staining revealed mitochondrial p53 translocation after tGCI in the hippocampal CA1 neurons [1].
  • The ability of the transcription factors p53, nuclear factor kappaB, and activator protein 1 (AP1) to bind to consensus DNA sequences was decreased markedly with zinc deficiency, as assayed by electrophoretic mobility-shift assays [28].
  • Mutant p53 and activated ras cDNA clones cooperate to fully transform primary rat embryo fibroblasts in cell culture, whereas neither cDNA alone results in the full transformation of these cells [29].
  • Using sucrose gradient ultracentrifugation, we have isolated low-density, Triton X-100-insoluble membrane domains from RBL-2H3 mucosal mast cells that contain several markers common to caveolae, including a src-family tyrosine kinase, p53/56lyn [30].

References

  1. Mitochondrial translocation of p53 mediates release of cytochrome c and hippocampal CA1 neuronal death after transient global cerebral ischemia in rats. Endo, H., Kamada, H., Nito, C., Nishi, T., Chan, P.H. J. Neurosci. (2006) [Pubmed]
  2. Targeted deletion of Puma attenuates cardiomyocyte death and improves cardiac function during ischemia-reperfusion. Toth, A., Jeffers, J.R., Nickson, P., Min, J.Y., Morgan, J.P., Zambetti, G.P., Erhardt, P. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  3. Hypoxia-activated apoptosis of cardiac myocytes requires reoxygenation or a pH shift and is independent of p53. Webster, K.A., Discher, D.J., Kaiser, S., Hernandez, O., Sato, B., Bishopric, N.H. J. Clin. Invest. (1999) [Pubmed]
  4. The adenovirus E4orf6 protein can promote E1A/E1B-induced focus formation by interfering with p53 tumor suppressor function. Nevels, M., Rubenwolf, S., Spruss, T., Wolf, H., Dobner, T. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  5. Chronic alcohol consumption induces genomic but not p53-specific DNA hypomethylation in rat colon. Choi, S.W., Stickel, F., Baik, H.W., Kim, Y.I., Seitz, H.K., Mason, J.B. J. Nutr. (1999) [Pubmed]
  6. Protein synthesis required to anchor a mutant p53 protein which is temperature-sensitive for nuclear transport. Gannon, J.V., Lane, D.P. Nature (1991) [Pubmed]
  7. Specific interaction between the p53 cellular tumour antigen and major heat shock proteins. Pinhasi-Kimhi, O., Michalovitz, D., Ben-Zeev, A., Oren, M. Nature (1986) [Pubmed]
  8. p53RDL1 regulates p53-dependent apoptosis. Tanikawa, C., Matsuda, K., Fukuda, S., Nakamura, Y., Arakawa, H. Nat. Cell Biol. (2003) [Pubmed]
  9. Tranilast inhibits vascular smooth muscle cell growth and intimal hyperplasia by induction of p21(waf1/cip1/sdi1) and p53. Takahashi, A., Taniguchi, T., Ishikawa, Y., Yokoyama, M. Circ. Res. (1999) [Pubmed]
  10. The NH2 terminus of influenza virus hemagglutinin-2 subunit peptides enhances the antitumor potency of polyarginine-mediated p53 protein transduction. Michiue, H., Tomizawa, K., Wei, F.Y., Matsushita, M., Lu, Y.F., Ichikawa, T., Tamiya, T., Date, I., Matsui, H. J. Biol. Chem. (2005) [Pubmed]
  11. p53-mediated upregulation of BAX gene transcription is not involved in Bax-alpha protein overexpression in the left ventricle of spontaneously hypertensive rats. Fortuño, M.A., Zalba, G., Ravassa, S., D'Elom, E., Beaumont, F.J., Fortuño, A., Díez, J. Hypertension (1999) [Pubmed]
  12. Nitric oxide diminishes apoptosis and p53 gene expression after renal ischemia and reperfusion injury. Martinez-Mier, G., Toledo-Pereyra, L.H., Bussell, S., Gauvin, J., Vercruysse, G., Arab, A., Harkema, J.R., Jordan, J.A., Ward, P.A. Transplantation (2000) [Pubmed]
  13. Cloning and characterization of two processed p53 pseudogenes from the rat genome. Lin, Y., Chan, S.H. Gene (1995) [Pubmed]
  14. Experimental glaucoma and optic nerve transection induce simultaneous upregulation of proapoptotic and prosurvival genes. Levkovitch-Verbin, H., Dardik, R., Vander, S., Nisgav, Y., Kalev-Landoy, M., Melamed, S. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  15. The role of Ca2+ on the DADS-induced apoptosis in mouse-rat hybrid retina ganglion cells (N18). Lin, H.L., Yang, J.S., Yang, J.H., Fan, S.S., Chang, W.C., Li, Y.C., Chung, J.G. Neurochem. Res. (2006) [Pubmed]
  16. Two molecularly distinct intracellular pathways to oligodendrocyte differentiation: role of a p53 family protein. Tokumoto, Y.M., Tang, D.G., Raff, M.C. EMBO J. (2001) [Pubmed]
  17. p53/58 binds COPI and is required for selective transport through the early secretory pathway. Tisdale, E.J., Plutner, H., Matteson, J., Balch, W.E. J. Cell Biol. (1997) [Pubmed]
  18. Immunohistochemical study of cell proliferation, Bcl-2, p53, and caspase-3 expression on preneoplastic changes induced by cadmium and zinc chloride in the ventral rat prostate. Arriazu, R., Pozuelo, J.M., Henriques-Gil, N., Perucho, T., Martín, R., Rodríguez, R., Santamaría, L. J. Histochem. Cytochem. (2006) [Pubmed]
  19. Haloperidol induces apoptosis via the sigma2 receptor system and Bcl-XS. Wei, Z., Mousseau, D.D., Dai, Y., Cao, X., Li, X.M. Pharmacogenomics J. (2006) [Pubmed]
  20. Effects of dietary folate on DNA strand breaks within mutation-prone exons of the p53 gene in rat colon. Kim, Y.I., Shirwadkar, S., Choi, S.W., Puchyr, M., Wang, Y., Mason, J.B. Gastroenterology (2000) [Pubmed]
  21. Posttranslational modification of the Ha-ras oncogene protein: evidence for a third class of protein carboxyl methyltransferases. Clarke, S., Vogel, J.P., Deschenes, R.J., Stock, J. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  22. Heat shock protein 84 forms a complex with mutant p53 protein predominantly within a cytoplasmic compartment of the cell. Sepehrnia, B., Paz, I.B., Dasgupta, G., Momand, J. J. Biol. Chem. (1996) [Pubmed]
  23. p53 status affects the rate of the onset but not the overall extent of doxorubicin-induced cell death in rat-1 fibroblasts constitutively expressing c-Myc. Han, J.W., Dionne, C.A., Kedersha, N.L., Goldmacher, V.S. Cancer Res. (1997) [Pubmed]
  24. Antitumour activity of a combined treatment with PMEDAP and docetaxel in the Prague inbred Sprague-Dawley/cub rat strain bearing T-cell lymphoma. Bobkov, K., Gut, I., Mandys, V., Holý, A., Votruba, I., Otová, B. Anticancer Res. (2001) [Pubmed]
  25. Activation of the transforming growth factor beta signaling pathway and induction of cytostasis and apoptosis in mammary carcinomas treated with the anticancer agent perillyl alcohol. Ariazi, E.A., Satomi, Y., Ellis, M.J., Haag, J.D., Shi, W., Sattler, C.A., Gould, M.N. Cancer Res. (1999) [Pubmed]
  26. Increased expression of Fas (CD95/APO-1) in adult rat brain after kainate-induced seizures. Tan, Z., Levid, J., Schreiber, S.S. Neuroreport (2001) [Pubmed]
  27. Differential effect of hydrogen peroxide and superoxide anion on apoptosis and proliferation of vascular smooth muscle cells. Li, P.F., Dietz, R., von Harsdorf, R. Circulation (1997) [Pubmed]
  28. Low intracellular zinc induces oxidative DNA damage, disrupts p53, NFkappa B, and AP1 DNA binding, and affects DNA repair in a rat glioma cell line. Ho, E., Ames, B.N. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  29. A mutant p53 protein is required for maintenance of the transformed phenotype in cells transformed with p53 plus ras cDNAs. Zambetti, G.P., Olson, D., Labow, M., Levine, A.J. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  30. Fc epsilon RI-mediated recruitment of p53/56lyn to detergent-resistant membrane domains accompanies cellular signaling. Field, K.A., Holowka, D., Baird, B. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
 
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