p53 and the regulation of hepatocyte apoptosis: implications for disease pathogenesis

Trends in Molecular Medicine

Volumn 15, Issue 11, 2009, Pages 531-541

  Amaral, Joana D ^a   Castro, Rui E ^a   Steer, Clifford J ^b   Rodrigues, Cecília M P ^a  

^a RESEARCH INSTITUTE FOR MEDICINES IMED ULISBOA   (Portugal)

^b UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN MDM2; PROTEIN P53; URSODEOXYCHOLIC ACID;

APOPTOSIS; CELLULAR DISTRIBUTION; DOWN REGULATION; GENE ACTIVATION; GENE MUTATION; GENE OVEREXPRESSION; GENETIC TRANSCRIPTION; HUMAN; LIVER CARCINOGENESIS; LIVER CARCINOMA; LIVER CELL; LIVER DISEASE; NONHUMAN; PATHOGENESIS; PROTEIN DEGRADATION; PROTEIN FUNCTION; PROTEIN PROCESSING; PROTEIN TARGETING; REVIEW; SIGNAL TRANSDUCTION;

APOPTOSIS; HEPATOCYTES; HUMANS; TUMOR SUPPRESSOR PROTEIN P53; URSODEOXYCHOLIC ACID;

EID: 70449109071     PISSN: 14714914     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.molmed.2009.09.005     Document Type: Review

References (104)

1. Vousden K.H., and Lane D.P. p53 in health and disease. Nat. Rev. Mol. Cell Biol. 8 (2007) 275-283
2. Joerger A.C., and Fersht A.R. Structural biology of the tumor suppressor p53. Annu. Rev. Biochem. 77 (2008) 557-582
3. Riley T., et al. Transcriptional control of human p53-regulated genes. Nat. Rev. Mol. Cell Biol. 9 (2008) 402-412
4. Balint E.E., and Vousden K.H. Activation and activities of the p53 tumor suppressor protein. Br. J. Cancer 85 (2001) 1813-1823
5. Green D.R., and Kroemer G. Cytoplasmic functions of the tumor suppressor p53. Nature 458 (2009) 1127-1130
6. Ashcroft M., and Vousden K.H. Regulation of p53 stability. Oncogene 18 (1999) 7637-7643
7. Pietsch E.C., et al. The p53 family and programmed cell death. Oncogene 27 (2008) 6507-6521
8. Kroemer G., et al. Mitochondrial membrane permeabilization in cell death. Physiol. Rev. 87 (2007) 99-163
9. Jeffers J.R., et al. Puma is an essential mediator of p53-dependent and -independent apoptotic pathways. Cancer Cell 4 (2003) 321-328
10. Bouvard V., et al. Tissue and cell-specific expression of the p53 target genes Bax, Fas, Mdm2 and Waf1/p21, before and following ionizing irradiation in mice. Oncogene 19 (2000) 649-660
11. Bennett M., et al. Cell surface trafficking of Fas: a rapid mechanism of p53-mediated apoptosis. Science 282 (1998) 290-293
12. Wu G.S., et al. KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor gene. Nat. Genet. 17 (1997) 141-143
13. Moroni M.C., et al. Apaf-1 is a transcriptional target for E2F and p53. Nat. Cell Biol. 3 (2001) 552-558
14. Hoffman W.H., et al. Transcriptional repression of the antiapoptotic survivin gene by wild type p53. J. Biol. Chem. 277 (2002) 3247-3257
15. Schuler M., et al. p53 induces apoptosis by caspase activation through mitochondrial cytochrome c release. J. Biol. Chem. 275 (2000) 7337-7342
16. Marchenko N.D., et al. Monoubiquitylation promotes mitochondrial p53 translocation. EMBO J. 26 (2007) 923-934
17. Speidel D., et al. Dissection of transcriptional and non-transcriptional p53 activities in the response to genotoxic stress. Oncogene 25 (2006) 940-953
18. Wolff S., et al. p53's mitochondrial translocation and MOMP action is independent of Puma and Bax and severely disrupts mitochondrial membrane integrity. Cell Res. 18 (2008) 733-744
19. Han M.K., et al. SIRT1 regulates apoptosis and Nanog expression in mouse embryonic stem cells by controlling p53 subcellular localization. Cell Stem Cell 2 (2008) 241-251
20. Chipuk J.E., et al. Puma couples the nuclear and cytoplasmic pro-apoptotic function of p53. Science 309 (2005) 1732-1735
21. Janicke R.U., et al. The dark side of a tumor suppressor: antiapoptotic p53. Cell Death Differ. 15 (2008) 959-976
22. Vousden K.H., and Lu X. Live or let die: the cell's response to p53. Nat. Rev. Cancer 2 (2002) 594-604
23. Wierod L., et al. Activation of the p53-p21(Cip1) pathway is required for CDK2 activation and S-phase entry in primary rat hepatocytes. Oncogene 27 (2008) 2763-2771
24. Erster S., et al. In vivo mitochondrial p53 translocation triggers a rapid first wave of cell death in response to DNA damage that can precede p53 target gene activation. Mol. Cell Biol. 24 (2004) 6728-6741
25. Xue W., et al. Senescence and tumor clearance is triggered by p53 restoration in murine liver carcinomas. Nature 445 (2007) 656-660
26. Leu J.I., and George D.L. Hepatic IGFBP1 is a prosurvival factor that binds to BAK, protects the liver from apoptosis and antagonizes the pro-apoptotic actions of p53 at mitochondria. Genes Dev. 21 (2007) 3095-3109
27. Qiao L., et al. Cyclin kinase inhibitor p21 potentiates bile acid-induced apoptosis in hepatocytes that is dependent on p53. Hepatology 36 (2002) 39-48
28. Zhang G., et al. Multiple cyclin kinase inhibitors promote bile acid-induced apoptosis and autophagy in primary hepatocytes via p53-CD95-dependent signaling. J. Biol. Chem. 283 (2008) 24343-24358
29. Harada K., et al. Increased expression of Waf1 in intrahepatic bile ducts in primary biliary cirrhosis relates to apoptosis. J. Hepatol. 34 (2001) 500-506
30. Salunga T.L., et al. Oxidative stress-induced apoptosis of bile duct cells in primary biliary cirrhosis. J. Autoimmun. 29 (2007) 78-86
31. Castro R.E., et al. Differential regulation of cyclin D1 and cell death by bile acids in primary rat hepatocytes. Am. J. Physiol. Gastrointest. Liver Physiol. 293 (2007) G327-334
32. Yang H., et al. Switch from Mnt-Max to Myc-Max induces p53 and cyclin D1 expression and apoptosis during cholestasis in mouse and human hepatocytes. Hepatology 49 (2009) 860-870
33. Oh S.H., et al. Changes in expression and immunolocalization of protein associated with toxic bile salts-induced apoptosis in rat hepatocytes. Arch. Toxicol. 77 (2003) 110-115
34. Farrell G.C., et al. Apoptosis in experimental NASH is associated with p53 activation and TRAIL receptor expression. J. Gastroenterol. Hepatol. 24 (2009) 443-452
35. Guo R., et al. Overexpression of aldehyde dehydrogenase-2 attenuates chronic alcohol exposure-induced apoptosis, change in Akt and Pim signaling in liver. Clin. Exp. Pharmacol. Physiol. 36 (2009) 463-468
36. Lasfer M., et al. Cadmium induces mitochondria-dependent apoptosis of normal human hepatocytes. Cell Biol. Toxicol. 24 (2008) 55-62
37. Fabregat I. Dysregulation of apoptosis in hepatocellular carcinoma cells. World J. Gastroenterol. 15 (2009) 513-520
38. Guan Y.S., et al. p53 gene in treatment of hepatic carcinoma: status quo. World J. Gastroenterol. 13 (2007) 985-992
39. El Far M.A., et al. Evaluation of serum levels of p53 in hepatocellular carcinoma in Egypt. Clin. Chem. Lab. Med. 44 (2006) 653-656
40. Wu, M. et al. (2009) Serum p53 protein and anti-p53 antibodies are associated with increased cancer risk: a case-control study of 569 patients and 879 healthy controls. Mol. Biol. Rep. Aug 20. [Epub ahead of print]
41. Guicciardi M.E., and Gores G.J. Apoptosis: a mechanism of acute and chronic liver injury. Gut. 54 (2005) 1024-1033
42. Beerheide W., et al. Downregulation of pro-apoptotic proteins Bax and Bcl-X(S) in p53 overexpressing hepatocellular carcinomas. Biochem. Biophys. Res. Commun. 273 (2000) 54-61
43. Min S.H., et al. New p53 target, phosphatase of regenerating liver 1 (PRL-1) downregulates p53. Oncogene 28 (2009) 545-554
44. Farazi P.A., et al. Cooperative interactions of p53 mutation, telomere dysfunction and chronic liver damage in hepatocellular carcinoma progression. Cancer Res. 66 (2006) 4766-4773
45. Cheng A.S., et al. COX-2 mediates hepatitis B virus X protein abrogation of p53-induced apoptosis. Biochem. Biophys Res. Commun. 374 (2008) 175-180
46. Olive K.P., et al. Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome. Cell 119 (2004) 847-860
47. Kim E., and Deppert W. Transcriptional activities of mutant p53: when mutations are more than a loss. J. Cell Biochem. 93 (2004) 878-886
48. Gudkov A.V., and Komarova E.A. The role of p53 in determining sensitivity to radiotherapy. Nat. Rev. Cancer 3 (2003) 117-129
49. Christophorou M.A., et al. The pathological response to DNA damage does not contribute to p53-mediated tumor suppression. Nature 443 (2006) 214-217
50. Komarov P.G., et al. A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science 285 (1999) 1733-1737
51. Chin L., et al. p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell 97 (1999) 527-538
52. Artandi S.E., et al. Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice. Nature 406 (2000) 641-645
53. Gonzalez-Suarez E., et al. Telomerase-deficient mice with short telomeres are resistant to skin tumorigenesis. Nat. Genet. 26 (2000) 114-117
54. Cosme-Blanco W., et al. Telomere dysfunction suppresses spontaneous tumorigenesis in vivo by initiating p53-dependent cellular senescence. EMBO Rep. 8 (2007) 497-503
55. Choudhury A.R., et al. Cdkn1a deletion improves stem cell function and lifespan of mice with dysfunctional telomeres without accelerating cancer formation. Nat. Genet. 39 (2007) 99-105
56. Schaetzlein S., et al. Exonuclease-1 deletion impairs DNA damage signaling and prolongs lifespan of telomere-dysfunctional mice. Cell 130 (2007) 863-877
57. Begus-Nahrmann Y., et al. p53 deletion impairs clearance of chromosomal-instable stem cells in ageing telomere-dysfunctional mice. Nat. Genet. 41 (2009) 1138-1143
58. Castedo M., et al. p53 - a pro-apoptotic signal transducer involved in AIDS. Biochem. Biophys Res. Commun. 331 (2005) 701-706
59. Beuers U. Drug insight: mechanisms and sites of action of ursodeoxycholic acid in cholestasis. Nat. Clin. Pract. Gastroenterol. Hepatol. 3 (2006) 318-328
60. Rodrigues C.M., et al. A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating mitochondrial membrane perturbation. J. Clin. Invest. 101 (1998) 2790-2799
61. Benz C., et al. Effect of tauroursodeoxycholic acid on bile acid-induced apoptosis in primary human hepatocytes. Eur. J. Clin. Invest. 30 (2000) 203-209
62. Paumgartner G., and Beuers U. Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited. Hepatology 36 (2002) 525-531
63. Schoemaker M.H., et al. Tauroursodeoxycholic acid protects rat hepatocytes from bile acid-induced apoptosis via activation of survival pathways. Hepatology 39 (2004) 1563-1573
64. Miura T., et al. Functional modulation of the glucocorticoid receptor and suppression of NF-κB-dependent transcription by ursodeoxycholic acid. J. Biol. Chem. 276 (2001) 47371-47378
65. Rodrigues C.M., et al. Ursodeoxycholic acid prevents cytochrome c release in apoptosis by inhibiting mitochondrial membrane depolarization and channel formation. Cell Death Differ. 6 (1999) 842-854
66. Rodrigues C.M., et al. Tauroursodeoxycholic acid prevents Bax-induced membrane perturbation and cytochrome c release in isolated mitochondria. Biochemistry 42 (2003) 3070-3080
67. Azzaroli F., et al. Ursodeoxycholic acid diminishes Fas-ligand-induced apoptosis in mouse hepatocytes. Hepatology 36 (2002) 49-54
68. Xie Q., et al. Effect of tauroursodeoxycholic acid on endoplasmic reticulum stress-induced caspase-12 activation. Hepatology 36 (2002) 592-601
69. Ozcan L., et al. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab. 9 (2009) 35-51
70. Solá S., et al. Nuclear translocation of UDCA by the glucocorticoid receptor is required to reduce TGF-β1-induced apoptosis in rat hepatocytes. Hepatology 42 (2005) 925-934
71. Castro R., et al. Bile acids as modulators of apoptosis. In: Sahu S. (Ed). Hepatotoxicity: From Genomics to in vitro and in vivo Models (2007), John Wiley & Sons 391-420
72. Amaral J.D., et al. p53 is a key molecular target of ursodeoxycholic acid in regulating apoptosis. J. Biol. Chem. 282 (2007) 34250-34259
73. Ramalho R.M., et al. Inhibition of the E2F-1/p53/Bax pathway by tauroursodeoxycholic acid in amyloid β-peptide-induced apoptosis of PC12 cells. J. Neurochem. 90 (2004) 567-575
74. Ringshausen I., et al. Mdm2 is critically and continuously required to suppress lethal p53 activity in vivo. Cancer Cell 10 (2006) 501-514
75. Serfaty L., et al. Ursodeoxycholic acid therapy and the risk of colorectal adenoma in patients with primary biliary cirrhosis: an observational study. Hepatology 38 (2003) 203-209
76. Tung B.Y., et al. Ursodiol use is associated with lower prevalence of colonic neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis. Ann. Intern. Med. 134 (2001) 89-95
77. Wali R.K., et al. Ursodeoxycholic acid and F(6)-D(3) inhibit aberrant crypt proliferation in the rat azoxymethane model of colon cancer: roles of cyclin D1 and E-cadherin. Cancer Epidemiol. Biomarkers Prev. 11 (2002) 1653-1662
78. Park H., et al. Ursodeoxycholic acid prevents apoptosis of mouse sensory neurons induced by cisplatin by reducing p53 accumulation. Biochem. Biophys. Res. Commun. 377 (2008) 1025-1030
79. Culmsee C., and Mattson M.P. p53 in neuronal apoptosis. Biochem. Biophys. Res. Commun. 331 (2005) 761-777
80. Tian G., et al. Multiple hepatic arterial injections of recombinant adenovirus p53 and 5-fluorouracil after transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: a pilot phase II trial. Anticancer Drugs 20 (2009) 389-395
81. Tian G., et al. A patient with huge hepatocellular carcinoma who had a complete clinical response to p53 gene combined with chemotherapy and transcatheter arterial chemoembolization. Anticancer Drugs 20 (2009) 403-407
82. Sagawa T., et al. Treatment of hepatocellular carcinoma by AdAFPep/rep, AdAFPep/p53 and 5-fluorouracil in mice. Hepatology 48 (2008) 828-840
83. Chen C.A., et al. Application of doxorubicin-induced rAAV2-p53 gene delivery in combined chemotherapy and gene therapy for hepatocellular carcinoma. Cancer Biol. Ther. 7 (2008) 303-309
84. Shangary S., and Wang S. Small molecule inhibitors of the Mdm2-p53 protein-protein interaction to reactivate p53 function: a novel approach for cancer therapy. Annu. Rev. Pharmacol. Toxicol. 49 (2009) 223-241
85. Logan I.R., et al. Analysis of the Mdm2 antagonist Nutlin-3 in human prostate cancer cells. Prostate 67 (2007) 900-906
86. Georgiev P., et al. Blocking the path to death: antiapoptotic molecules in ischemia/reperfusion injury of the liver. Curr. Pharm. Des. 12 (2006) 2911-2921
87. Matsusaka H., et al. Targeted deletion of p53 prevents cardiac rupture after myocardial infarction in mice. Cardiovasc. Res. 70 (2006) 457-465
88. Schafer T., et al. Inhibition of p53 protects liver tissue against endotoxin-induced apoptotic and necrotic cell death. FASEB J. 17 (2003) 660-667
89. Oh S.H., et al. Salvia miltiorrhiza inhibits biliary obstruction-induced hepatocyte apoptosis by cytoplasmic sequestration of p53. Toxicol. Appl. Pharmacol. 182 (2002) 27-33
90. Kim E., et al. Wild type p53 in cancer cells: when a guardian turns into a blackguard. Biochem. Pharmacol. 77 (2009) 11-20
91. Maier B., et al. Modulation of mammalian lifespan by the short isoform of p53. Genes Dev. 18 (2004) 306-319
92. Smith L., and Byers J.F. Gene therapy in the post-Gelsinger era. JONAS Healthc. Law Ethics Regul. 4 (2002) 104-110
93. Brooks C.L., et al. Mechanistic studies of Mdm2-mediated ubiquitination in p53 regulation. J. Biol. Chem. 282 (2007) 22804-22815
94. O'Keefe K., et al. Nucleocytoplasmic shuttling of p53 is essential for Mdm2-mediated cytoplasmic degradation but not ubiquitination. Mol. Cell Biol. 23 (2003) 6396-6405
95. Dyson N. The regulation of E2F by pRB-family proteins. Genes Dev. 12 (1998) 2245-2262
96. Bates S., et al. p14ARF links the tumor suppressors RB and p53. Nature 395 (1998) 124-125
97. Bykov V.J., and Wiman K.G. Novel cancer therapy by reactivation of the p53 apoptosis pathway. Ann. Med. 35 (2003) 458-465
98. Nemunaitis J., et al. Adenovirus-mediated p53 gene transfer in sequence with cisplatin to tumors of patients with non-small-cell lung cancer. J. Clin. Oncol. 18 (2000) 609-622
99. Bassett E.A., et al. Structural and functional basis for therapeutic modulation of p53 signaling. Clin. Cancer Res. 14 (2008) 6376-6386
100. Dudkina A.S., and Lindsley C.W. Small molecule protein-protein inhibitors for the p53-Mdm2 interaction. Curr. Top. Med. Chem. 7 (2007) 952-960
101. Vassilev L.T., et al. In vivo activation of the p53 pathway by small molecule antagonists of Mdm2. Science 303 (2004) 844-848
102. Issaeva N., et al. Small molecule RITA binds to p53, blocks p53-Hdm2 interaction and activates p53 function in tumors. Nat. Med. 10 (2004) 1321-1328
103. Yang Y., et al. Small molecule inhibitors of Hdm2 ubiquitin ligase activity stabilize and activate p53 in cells. Cancer Cell 7 (2005) 547-559
104. Amaral, J.D. et al. (2009) Bile acids: regulation of apoptosis by ursodeoxycholic acid. J. Lipid. Res. May 5. [Epub ahead of print]