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Structural insights into the transcription-independent apoptotic pathway of p53

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Reactivating the p53 pathway in tumors is an important strategyfor anticancer therapy. In response to diverse cellular stresses,the tumor suppressor p53 mediates apoptosis in a transcriptionindependentand transcription-dependent manner. Althoughextensive studies have focused on the transcription-dependentapoptotic pathway of p53, the transcription-independentapoptotic pathway of p53 has only recently been discovered. Molecular interactions between p53 and Bcl-2 family proteinsin the mitochondria play an essential role in the transcriptionindependentapoptosis of p53. This review describes the structuralbasis for the transcription-independent apoptotic pathwayof p53 and discusses its potential application to anticancer therapy.

Abstract

Reactivating the p53 pathway in tumors is an important strategyfor anticancer therapy. In response to diverse cellular stresses,the tumor suppressor p53 mediates apoptosis in a transcriptionindependentand transcription-dependent manner. Althoughextensive studies have focused on the transcription-dependentapoptotic pathway of p53, the transcription-independentapoptotic pathway of p53 has only recently been discovered. Molecular interactions between p53 and Bcl-2 family proteinsin the mitochondria play an essential role in the transcriptionindependentapoptosis of p53. This review describes the structuralbasis for the transcription-independent apoptotic pathwayof p53 and discusses its potential application to anticancer therapy.

참고문헌 (55)

  1. Harris, S. L., "The p53 pathway: positive and negative feedback loops", Oncogene, 24, pp.2899~2908 (2005)
  2. Sherr, C. J., "Principles of tumor suppression", Cell, 116, pp.235~246 (2004)
  3. Vogelstein, B., "Surfing the p53 network", Nature, 408, pp.307~310 (2000)
  4. Vousden, K. H., "Live or let die: the cell's response to p53", Nature Rev, 2, pp.594~604 (2002)
  5. Hollstein, M., "p53 mutations in human cancers", Science, 253, pp.49~53 (1991)
  6. Ventura, A., "Restoration of p53 function leads to tumour regression in vivo", Nature, 445, pp.661~665 (2007)
  7. Xue, W., "Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas", Nature, 445, pp.656~660 (2007)
  8. Martins, C. P., "Modeling the therapeutic efficacy of p53 restoration in tumors", Cell, 127, pp.1323~1334 (2006)
  9. Kussie, P. H., "Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain", Science, 274, pp.948~953 (1996)
  10. Chipuk, J. E., "PUMA couples the nuclear and cytoplasmic proapoptotic function of p53", Science, 309, pp.1732~1735 (2005)
  11. Chipuk, J. E., "Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis", Science, 303, pp.1010~1014 (2004)
  12. Jiang, P., "The Bad guy cooperates with good cop p53: Bad is transcriptionally up-regulated by p53 and forms a Bad", p53 complex at the mitochondria to induce apoptosis, 2006, pp.26, 9071~9082
  13. Leu, J. I., "Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex", Nat. Cell Biol, 6, pp.443~450 (2004)
  14. Mihara, M., "p53 has a direct apoptogenic role at the mitochondria", Mol. Cell, 11, pp.577~590 (2003)
  15. Tomita, Y., "WT p53, but not tumor-derived mutants, bind to Bcl2 via the DNA binding domain and induce mitochondrial permeabilization", J. Biol. Chem, 281, pp.8600~8606 (2006)
  16. Zhu, J., "Identification of a novel p53 functional domain that is necessary for mediating apoptosis", J. Biol. Chem, 273, pp.13030~13036 (1998)
  17. Chang, J., "Transactivation ability of p53 transcriptional activation domain is directly related to the binding affinity to TATA-binding protein", J. Biol. Chem, 270, pp.25014~25019 (1995)
  18. Gu, W., "Synergistic activation of transcription by CBP and p53", Nature, 387, pp.819~823 (1997)
  19. Uesugi, M., "The alpha-helical FXXPhiPhi motif in p53: TAF interaction and discrimination by MDM2", Proc. Natl. Aca. Sci. U.S.A, 96, pp.14801~14806 (1999)
  20. Ha, J. H., "Dual-site interactions of p53 protein transactivation domain with anti-apoptotic Bcl-2 family proteins reveal a highly convergent mechanism of divergent p53 pathways", J. Biol. Chem, 288, pp.7387~7398 (2013)
  21. Ha, J. H., "Molecular mimicry-based repositioning of nutlin-3 to anti-apoptotic Bcl-2 family proteins", J. Am. Chem. Soc, 133, pp.1244~1247 (2011)
  22. Bullock, A. N., "Quantitative analysis of residual folding and DNA binding in mutant p53 core domain: definition of mutant states for rescue in cancer therapy", Oncogene, 19, pp.1245~1256 (2000)
  23. Hey-Ryun Kim, "FGF-2 inhibits TNF-α mediated apoptosis through upregulation of Bcl2-A1 and Bcl-xL in ATDC5 cells", BMB Reports, 45(5), pp.287~292 (2012), 생화학분자생물학회
  24. Bing Qin, "MicroRNA let-7c inhibits Bcl-xl expression and regulates ox-LDL-induced endothelial apoptosis", BMB Reports, 45(8), pp.464~469 (2012), 생화학분자생물학회
  25. Kelekar, A, "Bcl-2-family proteins: the role of the BH3 domain in apoptosis", Trends Cell Biol, 8, pp.324~330 (1998)
  26. Youle, R. J., "The BCL-2 protein family: opposing activities that mediate cell death", Nat. Rev. Mol. Cell Biol, 9, pp.47~59 (2008)
  27. Lee, D. H., "Interaction of a putative BH3 domain of clusterin with anti-apoptotic Bcl-2 family proteins as revealed by NMR spectroscopy", Biochem. Biophys. Res. Commun, 408, pp.541~547 (2011)
  28. Sot, B., "Comparative biophysical characterization of p53 with the pro-apoptotic BAK and the anti-apoptotic BCL-xL", J. Biol. Chem, 282, pp.29193~29200 (2007)
  29. Hagn, F., "BclxL changes conformation upon binding to wild-type but not mutant p53 DNA binding domain", J. Biol. Chem, 285, pp.3439~3450 (2010)
  30. Petros, A. M., "Defining the p53 DNA-binding domain", Bcl-x(L)-binding interface using NMR, 2004, pp.559, 171~174
  31. Dong-Hwa Lee, "A Conserved Mechanism for Binding of p53 DNA-Binding Domain and Anti-Apoptotic Bcl-2 Family Proteins", Molecules and Cells, 37(3), pp.264~269 (2014), 한국분자세포생물학회[DOI]
  32. Chipuk, J. E., "Pharmacologic activation of p53 elicits Bax-dependent apoptosis in the absence of transcription", Cancer Cell, 4, pp.371~381 (2003)
  33. Sayan, B. S., "p53 is cleaved by caspases generating fragments localizing to mitochondria", J. Biol. Chem, 281, pp.13566~13573 (2006)
  34. Xu, H., "The N-terminal domain of tumor suppressor p53 is involved in the molecular interaction with the anti-apoptotic protein Bcl-Xl", Biochem. Biophys. Res. Commun, 341, pp.938~944 (2006)
  35. Xu, H., "The MDM2-binding region in the transactivation domain of p53 also acts as a Bcl-X(L)-binding motif", Biochemistry, 48, pp.12159~12168 (2009)
  36. Bharatham, N., "Molecular basis of Bcl-X(L)-p53 interaction: insights from molecular dynamics simulations", PLoS One, 6, pp.e26014~ (2011)
  37. Ha, J., "Molecular Interaction between a Bcl-2 Homolog from Kaposi Sarcoma Virus and p53", Bull. Korean Chem. Soc, 30, pp.1655~ (2009)
  38. Lee, M. S, "Structural basis for the conserved binding mechanism of MDM2-inhibiting peptides and anti-apopinsights into the transcription-independent apoptotic pathway of p53 Seung-Wook Chi 172 BMB Reports http:", Biochem. Biophys. Res. Commun, pp.2014, 445[DOI]
  39. Shin, J. S., "Targeting of p53 peptide analogues to anti-apoptotic Bcl-2 family proteins as revealed by NMR spectroscopy", Biochem. Biophys. Res. Commun, 443, pp.882~887 (2014)
  40. Fesik, S. W., "Promoting apoptosis as a strategy for cancer drug discovery", Nat. Rev. Cancer, 5, pp.876~885 (2005)
  41. Vassilev, L. T., "In vivo activation of the p53 pathway by small-molecule antagonists of MDM2", Science, 303, pp.844~848 (2004)
  42. Kojima, K., "Mdm2 inhibitor Nutlin-3a induces p53-mediated apoptosis by transcription- dependent and transcription-independent mechanisms and may overcome Atm-mediated resistance to fludarabine in chronic lymphocytic leukemia", Blood, 108, pp.993~1000 (2006)
  43. Vaseva, A. V., "The transcription-independent mitochondrial p53 program is a major contributor to nutlin-induced apoptosis in tumor cells", Cell Cycle, 8, pp.1711~1719 (2009)
  44. Saha, M. N., "Molecular mechanisms of nutlin-induced apoptosis in multiple myeloma: evidence for p53-transcription-dependent and -independent pathways", Cancer Biol. Ther, 10, pp.567~578 (2010)
  45. Kang, M. H, "Bcl-2 inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy", Clin. Cancer Res, 15, pp.1126~1132 (2009)
  46. Lessene, G., "BCL-2 family antagonists for cancer therapy", Nat. Rev. Drug Discov, 7, pp.989~1000 (2008)
  47. Oltersdorf, T, "An inhibitor of Bcl-2 family proteins induces regression of solid tumours", Nature, 435, pp.677~681 (2005)
  48. Konopleva, M., "Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia", Cancer Cell, 10, pp.375~388 (2006)
  49. van Delft, M. F., "The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak", Bax if Mcl-1 is neutralized, 2006, pp.10, 389~399
  50. Shin, J. S., "Structural insights into the dual-targeting mechanism of Nutlin-3. Biochem", Biophys. Res. Commun, 420, pp.48~53 (2012)
  51. Lee, E. F., "High-resolution structural characterization of a helical alpha", beta-peptide foldamer bound to the anti-apoptotic protein Bcl-xL, 2009, pp.48, 4318~4322
  52. Vassilev, L. T., "MDM2 inhibitors for cancer therapy", Trends Mol. Med, 13, pp.23~31 (2007)
  53. Kojima, K., "Concomitant inhibition of MDM2 and Bcl-2 protein function synergistically induce mitochondrial apoptosis in AML", Cell Cycle, 5, pp.2778~2786 (2006)
  54. Wade, M., "BH3 activation blocks Hdmx suppression of apoptosis and cooperates with Nutlin to induce cell death", Cell Cycle, 7, pp.1973~1982 (2008)
  55. Porter, J. R., "Profiling small molecule inhibitors against helix-receptor interactions: the Bcl-2 family inhibitor BH3I-1 potently inhibits p53", hDM2, 2010, pp.46, 8020~8022

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