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Gene Review

Tp53  -  tumor protein p53

Rattus norvegicus

Synonyms: Cellular tumor antigen p53, P53, Trp53, Tumor suppressor p53, p53
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Disease relevance of Tp53


Psychiatry related information on Tp53

  • The present results provide additional support for the view that NF-kappaB activation contributes to c-Myc and p53 induction and subsequent apoptosis in an excitotoxic model of Huntington's disease [6].
  • As up-regulation of p53 has been described as a common feature of several neurodegenerative disorders, including Alzheimer's disease, 2 and novel analogues (3-16) were synthesized to (i) assess the value of tetrahydrobenzothiazole analogues as neuroprotective agents and (ii) define the structural requirements for p53 inactivation [7].

High impact information on Tp53

  • The cells maintain high telomerase activity and p53- and Rb-dependent cell cycle checkpoint responses, and serum or genotoxic drugs induce them to acquire a senescence-like phenotype [8].
  • Baby rat kidney (BRK) cell lines transformed by E1A and a temperature-sensitive p53 [tsp53(val135)] undergo rapid apoptosis when p53 assumes the wild-type conformation at the permissive temperature [9].
  • In addition, there may exist at least two different mechanisms by which p53 can suppress cell-cycle progression, only one of which is dependent on p53-mediated transcription [9].
  • Primary rat embryo fibroblasts were transformed by a p53 mutant (alanine to valine change at amino acid 135) plus ras [10].
  • The S-phase cells appear to be immune to the p53 negative regulation of growth until they enter the next G1 period.(ABSTRACT TRUNCATED AT 250 WORDS)[10]

Chemical compound and disease context of Tp53


Biological context of Tp53


Anatomical context of Tp53


Associations of Tp53 with chemical compounds


Physical interactions of Tp53

  • More importantly, p38 kinase formed a complex with p53 after the treatment of CAPE for 0.5 hr [5].
  • The addition of exogenous ubiquitin to p53-Mdm2 complexes from apoptotic neurons restored p53 degradation [25].
  • These results suggest a prominent role of JNK and p38, as well as their downstream AP-1 binding activation and p53 phosphorylation in mediating glutamate excitotoxicity [26].

Enzymatic interactions of Tp53


Regulatory relationships of Tp53


Other interactions of Tp53

  • These data provide evidence that survival signals generated by PLD involve suppression of the p53 response pathway [28].
  • These data suggest a role of dysregulation of Bcl-2 family genes and, at least in atypical lesions, of p53 overexpression, in basal and AMPH-induced apoptosis in nodules and HCCs [31].
  • In this study we examined the role of p53 in the induction of apoptosis by TGF-beta1, and identified additional antiapoptosis targets for UDCA [18].
  • Thus, the stimulation of different p53 targets could be instrumental in determining the outcome of CXCR 4 activation on neuronal survival in neuro-inflammatory disorders [32].
  • A role for c-Jun N-terminal kinase 1 (JNK1), but not JNK2, in the beta-amyloid-mediated stabilization of protein p53 and induction of the apoptotic cascade in cultured cortical neurons [33].

Analytical, diagnostic and therapeutic context of Tp53

  • Survival assays with XTT (sodium 3'-1-(phenylaminocarbonyl)-3,4-tetrazolium-bis(4-methoxy-6-nitro)benzene sulfonic acid) and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) demonstrated that lack of p53 is initially protective against apoptosis [17].
  • Furthermore, Western blot analyses and double-immunofluorescent staining showed activation of c-Jun N-terminal kinase (JNK) and p53, and a localization of p53 in the dopaminergic neurons in the SN after thrombin, respectively [34].
  • Although we did not find a difference in the inhibitor of DNA binding/differentiation-2 (Id2) and c-Myc protein contents between the denervated and control muscles, the protein content of tumour suppressor p53 was significantly increased in both the nuclear and the cytosolic fractions with denervation [35].
  • These results suggested that arsenite induced apoptosis in the hepatocytes in vivo, through the enhancement of the activation of JNK and p38 MAPK caused by partial hepatectomy and the p53-dependent p21(WAF1/CIP1) protein expression [36].
  • To facilitate study of its role in carcinogenesis using a common animal model, we determined the structure of the rat p53 gene [37].


  1. Identification of genetic pathways activated by the androgen receptor during the induction of proliferation in the ventral prostate gland. Nantermet, P.V., Xu, J., Yu, Y., Hodor, P., Holder, D., Adamski, S., Gentile, M.A., Kimmel, D.B., Harada, S., Gerhold, D., Freedman, L.P., Ray, W.J. J. Biol. Chem. (2004) [Pubmed]
  2. Anoxic fibroblasts activate a replication checkpoint that is bypassed by E1a. Gardner, L.B., Li, F., Yang, X., Dang, C.V. Mol. Cell. Biol. (2003) [Pubmed]
  3. Glucose catabolism in cancer cells. The type II hexokinase promoter contains functionally active response elements for the tumor suppressor p53. Mathupala, S.P., Heese, C., Pedersen, P.L. J. Biol. Chem. (1997) [Pubmed]
  4. Regulation of the mitochondrial checkpoint in p53-mediated apoptosis confers resistance to cell death. Henry, H., Thomas, A., Shen, Y., White, E. Oncogene (2002) [Pubmed]
  5. Involvement of tumor suppressor protein p53 and p38 MAPK in caffeic acid phenethyl ester-induced apoptosis of C6 glioma cells. Lee, Y.J., Kuo, H.C., Chu, C.Y., Wang, C.J., Lin, W.C., Tseng, T.H. Biochem. Pharmacol. (2003) [Pubmed]
  6. Kainic acid-induced apoptosis in rat striatum is associated with nuclear factor-kappaB activation. Nakai, M., Qin, Z.H., Chen, J.F., Wang, Y., Chase, T.N. J. Neurochem. (2000) [Pubmed]
  7. Novel p53 inactivators with neuroprotective action: syntheses and pharmacological evaluation of 2-imino-2,3,4,5,6,7-hexahydrobenzothiazole and 2-imino-2,3,4,5,6,7-hexahydrobenzoxazole derivatives. Zhu, X., Yu, Q.S., Cutler, R.G., Culmsee, C.W., Holloway, H.W., Lahiri, D.K., Mattson, M.P., Greig, N.H. J. Med. Chem. (2002) [Pubmed]
  8. Lack of replicative senescence in cultured rat oligodendrocyte precursor cells. Tang, D.G., Tokumoto, Y.M., Apperly, J.A., Lloyd, A.C., Raff, M.C. Science (2001) [Pubmed]
  9. Essential role for p53-mediated transcription in E1A-induced apoptosis. Sabbatini, P., Lin, J., Levine, A.J., White, E. Genes Dev. (1995) [Pubmed]
  10. Cellular localization and cell cycle regulation by a temperature-sensitive p53 protein. Martinez, J., Georgoff, I., Martinez, J., Levine, A.J. Genes Dev. (1991) [Pubmed]
  11. Docosahexaenoic acid in combination with celecoxib modulates HSP70 and p53 proteins in prostate cancer cells. Narayanan, N.K., Narayanan, B.A., Bosland, M., Condon, M.S., Nargi, D. Int. J. Cancer (2006) [Pubmed]
  12. 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]
  13. Hyperglycemia activates p53 and p53-regulated genes leading to myocyte cell death. Fiordaliso, F., Leri, A., Cesselli, D., Limana, F., Safai, B., Nadal-Ginard, B., Anversa, P., Kajstura, J. Diabetes (2001) [Pubmed]
  14. Induction of p53-independent apoptosis by hygromycin B: suppression by Bcl-2 and adenovirus E1B 19-kDa protein. Chen, G., Branton, P.E., Shore, G.C. Exp. Cell Res. (1995) [Pubmed]
  15. Tp53-associated growth arrest and DNA damage repair gene expression is attenuated in mammary epithelial cells of rats fed whey proteins. Dave, B., Eason, R.R., Geng, Y., Su, Y., Badger, T.M., Simmen, R.C. J. Nutr. (2006) [Pubmed]
  16. A functional role for death proteases in s-Myc- and c-Myc-mediated apoptosis. Kagaya, S., Kitanaka, C., Noguchi, K., Mochizuki, T., Sugiyama, A., Asai, A., Yasuhara, N., Eguchi, Y., Tsujimoto, Y., Kuchino, Y. Mol. Cell. Biol. (1997) [Pubmed]
  17. Nerve growth factor withdrawal-mediated apoptosis in naive and differentiated PC12 cells through p53/caspase-3-dependent and -independent pathways. Vaghefi, H., Hughes, A.L., Neet, K.E. J. Biol. Chem. (2004) [Pubmed]
  18. Ursodeoxycholic acid modulates E2F-1 and p53 expression through a caspase-independent mechanism in transforming growth factor beta1-induced apoptosis of rat hepatocytes. Sola, S., Ma, X., Castro, R.E., Kren, B.T., Steer, C.J., Rodrigues, C.M. J. Biol. Chem. (2003) [Pubmed]
  19. Nitric oxide and superoxide induced p53 and Bax accumulation during mesangial cell apoptosis. Sandau, K., Pfeilschifter, J., Brüne, B. Kidney Int. (1997) [Pubmed]
  20. Multiple actions of pifithrin-alpha on doxorubicin-induced apoptosis in rat myoblastic H9c2 cells. Chua, C.C., Liu, X., Gao, J., Hamdy, R.C., Chua, B.H. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  21. Expression of mitochondria-dependent apoptosis genes (p53, Bax, and Bcl-2) in rat granulosa cells during follicular development. Choi, D., Hwang, S., Lee, E., Yoon, S., Yoon, B.K., Bae, D. J. Soc. Gynecol. Investig. (2004) [Pubmed]
  22. P53 mediates the apoptotic response to GTP depletion after renal ischemia-reperfusion: protective role of a p53 inhibitor. Kelly, K.J., Plotkin, Z., Vulgamott, S.L., Dagher, P.C. J. Am. Soc. Nephrol. (2003) [Pubmed]
  23. Role of p53 in cisplatin-induced tubular cell apoptosis: dependence on p53 transcriptional activity. Jiang, M., Yi, X., Hsu, S., Wang, C.Y., Dong, Z. Am. J. Physiol. Renal Physiol. (2004) [Pubmed]
  24. Modulation of nuclear steroid receptors by ursodeoxycholic acid inhibits TGF-beta1-induced E2F-1/p53-mediated apoptosis of rat hepatocytes. Solá, S., Castro, R.E., Kren, B.T., Steer, C.J., Rodrigues, C.M. Biochemistry (2004) [Pubmed]
  25. p53 accumulation due to down-regulation of ubiquitin: relevance for neuronal apoptosis. Tan, Z., Qu, W., Tu, W., Liu, W., Baudry, M., Schreiber, S.S. Cell Death Differ. (2000) [Pubmed]
  26. Regulation of c-Jun N-terminal kinase, p38 kinase and AP-1 DNA binding in cultured brain neurons: roles in glutamate excitotoxicity and lithium neuroprotection. Chen, R.W., Qin, Z.H., Ren, M., Kanai, H., Chalecka-Franaszek, E., Leeds, P., Chuang, D.M. J. Neurochem. (2003) [Pubmed]
  27. Mechanical stretch-induced apoptosis in smooth muscle cells is mediated by beta1-integrin signaling pathways. Wernig, F., Mayr, M., Xu, Q. Hypertension (2003) [Pubmed]
  28. Phospholipase D elevates the level of MDM2 and suppresses DNA damage-induced increases in p53. Hui, L., Abbas, T., Pielak, R.M., Joseph, T., Bargonetti, J., Foster, D.A. Mol. Cell. Biol. (2004) [Pubmed]
  29. E2F1-specific induction of apoptosis and p53 accumulation, which is blocked by Mdm2. Kowalik, T.F., DeGregori, J., Leone, G., Jakoi, L., Nevins, J.R. Cell Growth Differ. (1998) [Pubmed]
  30. Insulin-like growth factor-1 induces Mdm2 and down-regulates p53, attenuating the myocyte renin-angiotensin system and stretch-mediated apoptosis. Leri, A., Liu, Y., Claudio, P.P., Kajstura, J., Wang, X., Wang, S., Kang, P., Malhotra, A., Anversa, P. Am. J. Pathol. (1999) [Pubmed]
  31. Implication of Bcl-2 family genes in basal and D-amphetamine-induced apoptosis in preneoplastic and neoplastic rat liver lesions. De Miglio, M.R., Muroni, M.R., Simile, M.M., Calvisi, D.F., Tolu, P., Deiana, L., Carru, A., Bonelli, G., Feo, F., Pascale, R.M. Hepatology (2000) [Pubmed]
  32. Regulation of neuronal P53 activity by CXCR 4. Khan, M.Z., Shimizu, S., Patel, J.P., Nelson, A., Le, M.T., Mullen-Przeworski, A., Brandimarti, R., Fatatis, A., Meucci, O. Mol. Cell. Neurosci. (2005) [Pubmed]
  33. A role for c-Jun N-terminal kinase 1 (JNK1), but not JNK2, in the beta-amyloid-mediated stabilization of protein p53 and induction of the apoptotic cascade in cultured cortical neurons. Fogarty, M.P., Downer, E.J., Campbell, V. Biochem. J. (2003) [Pubmed]
  34. Thrombin induces nigral dopaminergic neurodegeneration in vivo by altering expression of death-related proteins. Choi, S.H., Lee, d.a. .Y., Ryu, J.K., Kim, J., Joe, E.H., Jin, B.K. Neurobiol. Dis. (2003) [Pubmed]
  35. Mitochondria-associated apoptotic signalling in denervated rat skeletal muscle. Siu, P.M., Alway, S.E. J. Physiol. (Lond.) (2005) [Pubmed]
  36. Arsenite induces apoptosis in hepatocytes through an enhancement of the activation of Jun N-terminal kinase and p38 mitogen-activated protein kinase caused by partial hepatectomy. Suzuki, T., Tsukamoto, I. Toxicol. Lett. (2006) [Pubmed]
  37. Structure of the rat p53 tumor suppressor gene. Hulla, J.E., Schneider, R.P. Nucleic Acids Res. (1993) [Pubmed]
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