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Pathway Description
p53 Signaling Pathway
Homo sapiens
Protein Pathway
Created: 2018-06-21
Last Updated: 2019-08-19
p53, named for its apparent molecular mass of 53 kilodaltons via SDS-PAGE analysis, is a protein that functions as a tumour suppressor and plays an important role in cell cycle regulation and cancer prevention. Over 50% of all cancers are theorized to involve p53-inactivating mutations. DNA damage, activated oncogenes, and oxidative stress can all produce stress signals to activate the p53 protein which is a transcriptional activator of >2500 p53-regulated genes. Activation of p53-regulated genes will lead to cellular senescence, cell cycle arrest, or apoptosis. Activated p53-regulated genes will also communicate with nearby cells for the purpose of DNA repair or feedback loop set-up that can either strengthen or weaken the stress responses of the p53 protein.
References
p53 Signaling Pathway References
Tanikawa C, Zhang YZ, Yamamoto R, Tsuda Y, Tanaka M, Funauchi Y, Mori J, Imoto S, Yamaguchi R, Nakamura Y, Miyano S, Nakagawa H, Matsuda K: The Transcriptional Landscape of p53 Signalling Pathway. EBioMedicine. 2017 Jun;20:109-119. doi: 10.1016/j.ebiom.2017.05.017. Epub 2017 May 18.
Pubmed: 28558959
Mirzayans R, Andrais B, Scott A, Murray D: New insights into p53 signaling and cancer cell response to DNA damage: implications for cancer therapy. J Biomed Biotechnol. 2012;2012:170325. doi: 10.1155/2012/170325. Epub 2012 Jul 15.
Pubmed: 22911014
Riley T, Sontag E, Chen P, Levine A: Transcriptional control of human p53-regulated genes. Nat Rev Mol Cell Biol. 2008 May;9(5):402-12. doi: 10.1038/nrm2395.
Pubmed: 18431400
Levine AJ, Oren M: The first 30 years of p53: growing ever more complex. Nat Rev Cancer. 2009 Oct;9(10):749-58. doi: 10.1038/nrc2723.
Pubmed: 19776744
Tanaka S, Louie DC, Kant JA, Reed JC: Frequent incidence of somatic mutations in translocated BCL2 oncogenes of non-Hodgkin's lymphomas. Blood. 1992 Jan 1;79(1):229-37.
Pubmed: 1339299
Tsujimoto Y, Croce CM: Analysis of the structure, transcripts, and protein products of bcl-2, the gene involved in human follicular lymphoma. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5214-8. doi: 10.1073/pnas.83.14.5214.
Pubmed: 3523487
Eguchi Y, Ewert DL, Tsujimoto Y: Isolation and characterization of the chicken bcl-2 gene: expression in a variety of tissues including lymphoid and neuronal organs in adult and embryo. Nucleic Acids Res. 1992 Aug 25;20(16):4187-92. doi: 10.1093/nar/20.16.4187.
Pubmed: 1508712
Apte SS, Mattei MG, Olsen BR: Mapping of the human BAX gene to chromosome 19q13.3-q13.4 and isolation of a novel alternatively spliced transcript, BAX delta. Genomics. 1995 Apr 10;26(3):592-4.
Pubmed: 7607685
Oltvai ZN, Milliman CL, Korsmeyer SJ: Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 1993 Aug 27;74(4):609-19. doi: 10.1016/0092-8674(93)90509-o.
Pubmed: 8358790
Shi B, Triebe D, Kajiji S, Iwata KK, Bruskin A, Mahajna J: Identification and characterization of baxepsilon, a novel bax variant missing the BH2 and the transmembrane domains. Biochem Biophys Res Commun. 1999 Jan 27;254(3):779-85. doi: 10.1006/bbrc.1998.0130.
Pubmed: 9920818
Zakut-Houri R, Bienz-Tadmor B, Givol D, Oren M: Human p53 cellular tumor antigen: cDNA sequence and expression in COS cells. EMBO J. 1985 May;4(5):1251-5.
Pubmed: 4006916
Lamb P, Crawford L: Characterization of the human p53 gene. Mol Cell Biol. 1986 May;6(5):1379-85. doi: 10.1128/mcb.6.5.1379.
Pubmed: 2946935
Harlow E, Williamson NM, Ralston R, Helfman DM, Adams TE: Molecular cloning and in vitro expression of a cDNA clone for human cellular tumor antigen p53. Mol Cell Biol. 1985 Jul;5(7):1601-10. doi: 10.1128/mcb.5.7.1601.
Pubmed: 3894933
Savitsky K, Sfez S, Tagle DA, Ziv Y, Sartiel A, Collins FS, Shiloh Y, Rotman G: The complete sequence of the coding region of the ATM gene reveals similarity to cell cycle regulators in different species. Hum Mol Genet. 1995 Nov;4(11):2025-32. doi: 10.1093/hmg/4.11.2025.
Pubmed: 8589678
Vorechovsky I, Rasio D, Luo L, Monaco C, Hammarstrom L, Webster AD, Zaloudik J, Barbanti-Brodani G, James M, Russo G, et al.: The ATM gene and susceptibility to breast cancer: analysis of 38 breast tumors reveals no evidence for mutation. Cancer Res. 1996 Jun 15;56(12):2726-32.
Pubmed: 8665503
Platzer M, Rotman G, Bauer D, Uziel T, Savitsky K, Bar-Shira A, Gilad S, Shiloh Y, Rosenthal A: Ataxia-telangiectasia locus: sequence analysis of 184 kb of human genomic DNA containing the entire ATM gene. Genome Res. 1997 Jun;7(6):592-605. doi: 10.1101/gr.7.6.592.
Pubmed: 9199932
Tamborini E, Della Torre G, Lavarino C, Azzarelli A, Carpinelli P, Pierotti MA, Pilotti S: Analysis of the molecular species generated by MDM2 gene amplification in liposarcomas. Int J Cancer. 2001 Jun 15;92(6):790-6. doi: 10.1002/ijc.1271.
Pubmed: 11351297
Honda R, Tanaka H, Yasuda H: Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett. 1997 Dec 22;420(1):25-7. doi: 10.1016/s0014-5793(97)01480-4.
Pubmed: 9450543
Sharp DA, Kratowicz SA, Sank MJ, George DL: Stabilization of the MDM2 oncoprotein by interaction with the structurally related MDMX protein. J Biol Chem. 1999 Dec 31;274(53):38189-96. doi: 10.1074/jbc.274.53.38189.
Pubmed: 10608892
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