PUMA, a critical mediator of cell death - one decade on from its discovery

• Autorzy: Hikisz P. , Kilianska Z. M.
• Języki publikacji: EN

Abstrakty

EN

PUMA (p53 upregulated modulator of apoptosis) is a pro-apoptotic member of the BH3-only subgroup of the Bcl-2 family. It is a key mediator of p53-dependent and p53-independent apoptosis and was identified 10 years ago. The PUMA gene is mapped to the long arm of chromosome 19, a region that is frequently deleted in a large number of human cancers. PUMA mediates apoptosis thanks to its ability to directly bind known anti-apoptotic members of the Bcl-2 family. It mainly localizes to the mitochondria. The binding of PUMA to the inhibitory members of the Bcl-2 family (Bcl-2-like proteins) via its BH3 domain seems to be a critical regulatory step in the induction of apoptosis. It results in the displacement of the proteins Bax and/or Bak. This is followed by their activation and the formation of pore-like structures on the mitochondrial membrane, which permeabilizes the outer mitochondrial membrane, leading to mitochondrial dysfunction and caspase activation. PUMA is involved in a large number of physiological and pathological processes, including the immune response, cancer, neurodegenerative diseases and bacterial and viral infections.

Słowa kluczowe

EN

carcinogenesis; apoptosis; protein; Bcl-2 family; transcription factor; p53 protein upregulated modulator; cancer; human disease

• Wydawca: -
• Czasopismo: Cellular and Molecular Biology Letters
• Rocznik: 2012
• Tom: 17
• Numer: 4
• Opis fizyczny: p.646-669,fig.,ref.

Twórcy

autor

Hikisz P.

• Department of Thermobiology, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland

autor

Kilianska Z. M.

Bibliografia

• 1. Green, D.R. and Reed, J.C. Mitochondria and apoptosis. Science 281 (1998) 1309-1312.
• 2. Zhivotovsky, B. and Orrenius, S. Cell cycle and cell death in disease: past, present and future. J. Intern. Med. 268 (2010) 395-409.
• 3. Caroppi, P., Sinibaldi, F., Fiorucci, L. and Santucci, R. Apoptosis and human diseases: mitochondrion damage and lethal role of released cytochrome c as proapoptotic protein. Curr. Med. Chem. 16 (2009) 4058- 4065.
• 4. Plati, J. and Khosravi-Far, R. Apoptotic cell signaling in cancer progression and therapy. Integr. Biol. 3 (2011) 279-296.
• 5. Evan, G. and Vousden, K.M. Proliferation, cell cycle and apoptosis in cancer. Nature 111 (2001) 342-348.
• 6. Green, D.R. Apoptotic pathway: paper wraps stone blunts scissors. Cell 102 (2000) 1-4.
• 7. Hengartner, M.O. The biochemistry of apoptosis. Nature 407 (2000) 770-776.
• 8. Green, D.R. and Evan, G.J. A matter of life and death. Cancer Cell 1 (2002) 19-30.
• 9. Mohamed, N., Gutierrez, A., Nunez, M., Cocca, C., Marit, G., Cricco, G., Medina, V., Rivera, E. and Bergoc, R. Mitochondrial apoptotic pathways. Biocell 29 (2005) 149-161.
• 10. van Gurp, M., Festjens, N., van Loo, G., Saelens, X. and Vandenabeele, P. Mitochondrial intermembrane proteins in cell death. Biochem. Biophys. Res. Commun. 304 (2003) 487-497.
• 11. Cain, K., Bratton, S.B., Langlais, C., Walker, G., Brown, D.G., Sun, X.M. and Cohen, G.M. Apaf-1 oligomerizes into biologically active approximately 700-kDa and inactive approximately 1.4 MDa apoptosome complex. J. Biol. Chem. 275 (2000) 6067-6070.
• 12. Hill, M.M., Adrian, C. and Martin, S.J. Portrait of a killer: the mitochondrial apoptosome emerges from the shadows. Mol. Interv. 3 (2003) 19-26.
• 13. Riedl, S.J. and Salvesen, G.S. The apoptosome: signaling platform of cell death. Nat. Rev. Mol. Cell. Biol. 8 (2007) 405-413.
• 14. Borner, C. The Bcl-2 protein family: sensors and checkpoints for life-ordeath decisions. Mol. Immunol. 39 (2003) 615-647.
• 15. Adams, J.M. and Cory, S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene 26 (2007) 1324-1337.
• 16. Lanave, C., Santamaria, M. and Saccone, C. Comparative genomics: the evolutionary history of the Bcl-2 family. Gene 333 (2004) 71-79.
• 17. Willis, S.N. and Adams, J.M. Life in the balance: how BH3-only proteins induce apoptosis. Curr. Opin. Cell Biol. 17 (2005) 617-625.
• 18. Lomonosova, E. and Chinnadurai, G. BH3-only proteins in apoptosis and beyond: an overview. Oncogene 27 (2008) 2-19.
• 19. Letai, A., Bassik, M.C., Walensky, L.D., Sorcinelli, M.D., Weiler, S. and Korsmeyer, S.J. Distinct BH3 domains either sensitize or acrivate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell 2 (2002) 183-192.
• 20. Chipuk, J.E., Moldoveanu, T., Llambi, F., Parsons, M.J. and Green, D.R. The BCL-2 family reunion. Mol. Cell 37 (2010) 299-310.
• 21. Elkholi, R., Floros, K.V. and Chipuk, J.E. The role of BH3-only proteins in tumor cell development, signaling and treatment. Genes Cancer 2 (2011) 523-537.
• 22. Fricker, M., O’Prey, J., Tolkovsy, A.M and Ryan, K.M. Phosphorylation of Puma modulates its apoptotic function by regulating protein stability. Cell Death Dis. 1 (2010) DOI: e59; doc: 10.1038/cddis. 2010.38.
• 23. Jeffers, J.R., Parganas, E., Lee, Y., Yang, C., Wang, J., Brennan, J., MacLean, K.H., Han, J., Chittenden, T., Ihle, J.N., McKinnon, P.J., Cleveland, J.L. and Zambetti, G.P. Puma is an essential mediator of p53- dependent and -independent apoptotic pathways. Cancer Cell 4 (2003) 321-328.
• 24. Yu, J. and Zhang, L. PUMA, a potent killer with or without p53. Oncogene 27 (2008) S71-S83.
• 25. Yu, J., Zhang, L., Hwang, P.M., Kinzler, K.W. and Vogelstein, B. PUMA induces the rapid apoptosis of colorectal cancer cells. Mol. Cell. 7 (2001) 673-682.
• 26. Nakano, K. and Vousden, K.H. PUMA, a novel proapoptotic gene, is induced by p53. Mol. Cell. 7 (2001) 683-694.
• 27. Han, J., Flemington, C., Houghton, A.B., Gu, Z., Zambetti, G.P., Lutz, R.J., Zhu, L. and Chittenden, T. Expression of bbc3, a pro-apoptotic BH3-only gene, is regulated by diverse cell death and survival signals. Proc. Natl. Acad. Sci. USA 98 (2001) 11318-11323.
• 28. Yu, J., Wang, Z., Kinzler, K.W., Vogelstein, B. and Zhang, L. PUMA mediates the apoptotic response to p53 in colorectal cancer cells. Proc. Natl. Acad. Sci. USA 100 (2003) 1931-1936.
• 29. Yee, K.S. and Vousden, K.H. Contribution of membrane localization to the apoptotic activity of PUMA. Apoptosis 13 (2008) 87-95.
• 30. Day, C.L., Smits, C., Fan, C.F., Lee, E.F., Fairlie, W.D. and Hinds, M.G. Structure of the BH3 domains from the p53-inducible BH3-only proteins Noxa and Puma in complex with Mcl-1. J. Mol. Biol. 380 (2008) 958-971.
• 31. Cregan, S.P., Arbour, N.A., Maclaurin, J.G., Callaghan, S.M., Fortin, A., Cheung, E.C., Guberman, D.S., Park, D.S. and Slack, R.S. p53 activation domain 1 is essential for PUMA upregulation and p53-mediated neuronal cell death. J. Neurosci. 24 (2004) 10003-10012.
• 32. Wang, X., Wang, J., Lin, S., Geng, J., Wang, J. and Jiang., B. Sp1 is involved in H2O2-induced PUMA gene expression and apoptosis in colorectal cancer cells. J. Exp. Clin. Cancer Res. 24 (2008) 27-44.
• 33. Ming, L., Wang, P., Bank, A., Yu, J. and Zhang, L. PUMA dissociated Bax and Bcl-XL to induce apoptosis in colon cancer cells. J. Bioch. Chem. 28 (2006) 16034-16042.
• 34. Chipuk, J.E, Bouchier-Hayes, L., Kuwana, T., Newmayer, D.D. and Green, D.R. PUMA couples the nucler and cytoplasmic proapoptotic function of p53. Science 309 (2005) 1732-1735.
• 35. Zhang, C., Junxia, Z., Zhang, A., Wang, Y., Han, L., You, Y., Pu, P. and Kang, C. PUMA is a novel target of miR-221/222 in human epithelial cancers. Int. J. Oncol. 37 (2010) 1621-1626.
• 36. Zhang, C., Zhang, J., Zhang, A., Shi, Z., Han, L., Jia, Z., Yang, W., Wang, G., Jiang, T., You, Y., Pu, P., Cheng, J. and Kang, C. MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma. Mol. Cancer 9 (2010) 1-9.
• 37. Jabbour, A.M., Daunt, C.P., Green, B.D., Vogel, S., Gordon, L., Lee, R.S., Silke, N., Pearson, R.B., Vandenberg, C.J., Kelly, P.N., Nutt, S.L., Strasser, A., Borner, C. and Ekert, P.G. Myeloid progenitor cells lacking p53 exhibit delayed up-regulation of Puma and prolonged survival after cytokine deprivation. Blood 115 (2010) 344-352.
• 38. Ming, L., Sakaida, T., Yue, W., Jha, A., Zhang L. and Yu J. Sp1 and p73 activate PUMA following serum starvation. Carcinogenesis 29 (2008) 1878-1884.
• 39. Ray, R.M., Bhattacharya, S. and Johnson, L.R. Mdm2 inhibition induces apoptosis in p53 deficient human colon cancer cells by activating p73- and E2F1-mediated expression of PUMA and Siva-1. Apoptosis 16 (2011) 35-44.
• 40. You, H., Pellegrini, M., Tsuchihara, K., Yamamoto, K., Häcker, G., Erlacher, M., Villunger, A. and Mak T.W. FOXO3a-dependent regulation of Puma in response to cytokine/growth factor withdrawal. J. Exp. Med. 203 (2006) 1657-1663.
• 41. Dudgeon, C., Wang, P., Sun, X., Peng, R., Sun, Q., Yu, J. and Zhang, L. PUMA induction by FoxO3a mediates the anticancer activities of the broadrange kinase inhibitor UCN-01. Mol. Cancer Ther. 9 (2010) 2893-2902.
• 42. Hershko, T. and Ginsberg, D. Up-regulation of Bcl-2 homology 3 (BH3)- only proteins by E2F1 mediates apoptosis. J. Biol. Chem. 279 (2004) 8627- 8634.
• 43. Wu ,B., Qiu, W., Wang, P., Yu, H., Cheng, T., Zambetti, G.P., Zhang, L. and Yu J. p53 independent induction of PUMA mediates intestinal apoptosis in response to ischaemia-reperfusion. Gut 56 (2007) 645-654.
• 44. Li, J., Lee, B. and Lee A.S. Endoplasmic reticulum stress-induced apoptosis: multiple pathways and activation of p53-up-regulated modulator of apoptosis (PUMA) and NOXA by p53. J. Biol. Chem. 281 (2006) 7260- 7270.
• 45. Nickson, P., Toth, A. and Erhardt, P. PUMA is critical for neonatal cardiomyocyte apoptosis induced by endoplasmic reticulum stress. Cardiovasc. Res. 73 (2007) 48-56.
• 46. Webster, K.A. Puma joins the battery of BH3-only proteins that promote death and infarction during myocardial ischemia. Am. J. of Physiol. Heart Circ. Physiol. 291 (2006) 20-22.
• 47. Toth, A., Jeffers, J.R., Nickson, P., Min, J-Y., Morgan, J.P., Zambetti, G.P. and Erhardt, P. Targeted deletion of Puma attenuates cardiomyocyte death and improves cardiac function during ischemia-reperfusion. Am. J. Physiol. Heart Circ. Physiol. 291 (2006) 52-60.
• 48. Cazanave, S.C., Elmi, N.A., Akazawa, Y., Bronk, S.F., Mott, J.L. and Gores, G.J. CHOP and AP-1 cooperatively mediate PUMA expression during lipoapoptosis. Am. J. Physiol. Gastrointest. Liver Physiol. 299 (2010) 236-243.
• 49. Fernandez, P.C., Frank, S.R., Wang, L., Schroeder, M., Liu, S, Greene, J., Cocito, A. and Amati B. Genomic targets of the human c-Myc protein. Genes Dev. 17 (2003) 1115-1129.
• 50. Garrison, S.P., Jeffers, J.R., Yang, C., Nilsson, J.A., Hall, M.A., Rehg, J.E., Yue, W., Yu, J., Zhang, L., Onciu, M., Sample, J.T., Cleveland, J.L. and Zambetti, G.P. Selection against PUMA gene expression in Myc-driven Bcell lymphomagenesis. Mol. Cell. Biol. 28 (2008) 5391-5402.
• 51. Happo, L., Strasser, A. and Scott, C.L. BH3-only Proteins. in: Cell Death (Melino, G. and Vaux, D., Ed.), 1th edition, John Wiley&Sons – Ltd, 2010, 75-90.
• 52. Erlacher, M., Michalak, E.M., Strasser, A. and Villunger, A. The BH3-only proteins Puma and Noxa: Two Brothers in Arms. in: Apoptosis and Cancer Therapy: From Cutting-edge Science to Novel Therapeutic Concepts, (Debatin, K.M. and Fulda, S., Ed.), Wiley-VCH Verlag GmbH, Weinheim, Germany. DOI: 10.1002/9783527619665.ch13, 2008, 379-402.
• 53. Lozano, G. and Zambetti, G.P. What have animals models taught us about the p53 pathway? J. Pathol. 205 (2005) 206-220.
• 54. Zapaśnik, M. and Cymerys, J.M. p53 protein – guardian of the genome in the viral infection. Post. Biol. Kom. 36 (2009) 565-582.
• 55. Michalak, E.M., Villunger, A., Adams, J.M. and Strasser, A. In several cell types tumour suppressor p53 induces apoptosis largely via Puma but Noxa can contribute. Cell Death Differ. 15 (2008) 1019-1029.
• 56. Qiu, W., Carson-Walter, E.B., Liu, H., Epperly, M., Greenberger, J.S., Zambetti, G.P., Zhang, L., Yu, J. PUMA regulates intestinal progenitor cell radiosensitivity and gastrointestinal syndrome. Cell Stem Cell 2 (2008) 576-583.
• 57. Wang, P., Yu, J. and Zhang, L. The nuclear function of p53 is required for PUMA-mediated apoptosis induced by DNA damage. Proc. Natl. Acad. Sci. USA 104 (2007) 4054-4059.
• 58. Charvet, C., Wissler, M., Brauns-Schubert, P., Wang, S-J., Tang, Y., Sigloch, F.C., Mellert, H., Brandenburg, M., Lindner, S.E., Breit, B., Green, D.R., McMahon, S.B., Borner, C., Gu, W. and Maurer U. Phosphporylation of Tip60 by GSK-3 determines the induction of PUMA and apoptosis by p53. Mol. Cell. 42 (2011) 584-596.
• 59. Tang, Y., Luo, J., Zhang, W. and Gu, W. Tip60-dependent acetylation of p53modulates the decision between cell-cycle arrest and apoptosis. Mol. Cell 24 (2006) 827-839.
• 60. Sykes, S.M., Mellert, H.S., Holbert, M.A., Li, K., Marmorstein, R., Lane, W.S. and McMahon, S.B. Acetylation of the p53 DNA binding domain regulates apoptosis induction. Mol. Cell 24 (2006) 841-851.
• 61. Ibrahim, S.H., Akazawa, Y., Cazanave, S.C., Bronk, S.F., Elmi, N.A., Werneburg, N.W., Billadeau, D.D. and Gores, G.J. Glycogen synthase kinase-3 (GSK-3) inhibition attenuates hepatocyte lipoapoptosis. J. Hepatol. 54 (2011) 765-772.
• 62. Hetz, C. and Glimcher, L. The daily job of night killers: alternative roles of the BCL-2 family in organelle physiology. Trends Cell Biol. 18 (2007) 38-44.
• 63. Luo, X., He, Q., Huang, Y. and Sheikh, M.S. Transcriptional upregulation of PUMA modulates endoplasmic reticulum calcium pool depletioninduced apoptosis via Bax activation. Cell Death Differ. 12 (2005) 1310-1318.
• 64. Jiang, C.C., Lucas, K., Avery-Kiejda, K.A., Wade, M., deBock, C.E., Thorne, R.F., Allen, J., Hersey, P. and Zhang, X.D. Up-regulation of Mcl-1 is critical for survival of human melanoma cells upon endoplasmic reticulum stress. Cancer Res. 68 (2008) 6708-6717.
• 65. Wei, J., O’Brien, D., Vilgelm, A., Piazuelo, M.B., Correa, P., Washinghton, M.K., El-Rifai, W., Peek, R.M. and Zaika A. Interaction of Helicobacter pylori with gastric epithelial cells is mediated by the p53 protein family. Gastroenterology 134 (2008) 1412-1423.
• 66. Perfettini, J-L., Roumier, T., Casted, M., Larochette, N., Boya, P., Raynal, B., Lazar, V., Ciccosanti, F., Nardacci, R., Penninger, J., Piacentini, M. and Kroemer, G. NF-κB and p53 qre the dominant apoptosis-inducing transcription factors elicited by the HIV-1 envelope. J. Exp. Med. 199 (2004) 629-640.
• 67. Rodrigues, R., Paranhos-Baccala, G., Vernet, G. and Peyrefitte, C.N. Crimean-congo hemorrhagic fever virus-infected hepatocytes induced ERstress and apoptosis crosstalk. PLoS 7 (2012) 1-11.
• 68. Bauer, A., Villunger, A., Labi, V., Fischer, S.F., Strasser, A., Wagner, H., Schmid, R.M. and Häcker, G. The NF-κB regulator Bcl-3 and the BH3-only proteins Bim and Puma control the death of activated T cells. Proc. Natl. Acad. Sci. USA 103 (2006) 10979-10984.
• 69. Fisher, S.F., Belz, G.T. and Strasser, A. BH3-only protein Puma contributes to death of antigen-specific T cells during shutdown of an immune response to acute viral infection. Proc. Natl. Acad. Sci. USA 105 (2008) 3035-3040.
• 70. Häcker, G., Bauer, A. and Villunger , A. Apoptosis in activated T cells: what are the triggers, and what the signal transducers? Cell Cycle 5 (2006) 2421- 2424.
• 71. Hildeman, D., Jorgensen, T., Kappler, J. and Marrack P. Apoptosis and the homeostatic control of immune responses. Curr. Opin. Immunol. 19 (2007) 516-521.
• 72. Steckley, D., Karajgikar, M., Dale, L.B., Fuerth, B., Swan, P., DrummondMain, C., Poulter, M.O., Ferguson, S.S., Strasser, A. and Cregan, S.P. Puma is a dominant regulator of oxidative stress induced Bax activation and neuronal apoptosis. J. Neurosci. 27 (2007) 12989 -12999.
• 73. Sandow, J.J. Regulation of the BH3-only protein PUMA by growth factor signalling. Ph.D. Thesis of the University of Adelaide, School of Medicine, 2011, 1-144.
• 74. Dewson, G. and Kluck, R.M. Mechanisms by which Bak and Bax permeabilise mitochondria during apoptosis. J. Cell Sci. 122 (2009) 2801- 2808.
• 75. Häcker, G. and Weber A. BH3-only proteins trigger cytochrome c release, but how? Arch. Biochem. Biophys. 462 (2007) 150-155.
• 76. Kim, H., Tu, H.C., Ren, D., Takeuchi, O., Jeffers, J.R. , Zambetti, G.P., Hsieh, J.J. and Cheng, E.H. Stepwise activation of BAX and BAK by tBID, BIM, and PUMA initiates mitochondrial apoptosis. Mol. Cell 36 (2009) 487-499.
• 77. Gallenne, T., Gautier, F., Oliver, L., Hervouet, E., Noël, B., Hickman, J.A., Geneste, O., Cartron, P.F., Vallette, F.M., Manon, S. and Juin, P. Bax activation by the BH3-only protein Puma promotes cell dependence on antiapoptotic Bcl-2 family members. J. Cell Biol. 185 (2009) 279-290.
• 78. Kuwana, T., Bouchier-Hayes, L., Chipuk, J.E., Bonzon, C., Sullivan, B.A., Green, D.,R. and Newmeyer, D.D. BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly. Mol. Cell 17 (2005) 525-535.
• 79. Westphalm D., Dewson, G., Czabotar, P.E. and Kluck, R.M. Molecular biology of Bax and Bak activation and action. Biochim. Biophys. Acta 1813 (2011) 521-531.
• 80. Lindsay, J., Esposti, M.D. and Gilmore, A.P. Bcl-2 proteins and mitochondria-specificity in membrane targeting for death. Biochim. Biophys. Acta 1813 (2011) 532-539.
• 81. Ghiotto, F., Fais, F. and Bruno, S. BH3-Only Proteins: The death puppeteer’s wires. Cytometry A 77 (2010) 11-21.
• 82. Giam, M., Huang, D.S.C. and Bouillet, P. BH3-only proteins and their roles in programmed cell death. Oncogene 27 (2009) 128-136.
• 83. Shamas-Din, A., Brahmbhatt, H., Leber, B. and Andrews, D.W. BH3-only proteins: orchestrators of apoptosis. Biochim. Biophys. Acta 1813 (2010) 508-520.
• 84. Leber, B., Lin, J. and Andrews, D. W. Embedded Together: the life and death consequences of interaction of the Bcl-2 family with membranes. Apoptosis 12 (2007) 897-911.
• 85. Chipuk, J.E. and Green, D.R. How do BCL-2 proteins induce mitochondria outer membrane permeabilization? Trends Cell Biol. 18 (2008) 157-164.
• 86. Shore, G.C. Apoptosis: it’s BAK to VDAC. EMBO Rep. 10 (2009) 1311-1313.
• 87. Gavathiotis, E., Suzuki, M., Davis, M.L., Pitter, K., Bird, G.H., Katz, S.G., Tu, H.C., Kim, H., Cheng, E.H., Tjandra, N. and Walensky, L.D. BAX activation is initiated at a novel interaction site. Nature 455 (2008) 1076-81.
• 88. Willis, S.N., Fletcher, J.I., Kaumann, T., van Delft, M.F., Chen, L., Czabotar, P.E., Lerino, H., Lee, E.F., Fairlie, W.D., Bouillet, P., Strasser, A., Kluck, R.M., Adams, J.M. and Huang, D.C.S. Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science 315 (2007) 856-859.
• 89. Jabbour, A.M., Heraud, J.E., Daunt, C.P., Kaufmann, T., Sandow, J., O’Reilly, L.A., Callus, B.A., Lopez, A., Strasser, A., Vaux, D.L. and Ekert, P.G. Puma indirectly activates Bax to cause apoptosis in the absence of Bid or Bim. Cell Death Differ. 16 (2009) 555-563.
• 90. Chipuk, J.E., Fisher, J.C., Dillon, C.P., Kriwacki, R.W., Kuwana, T. and Green, D.R. Mechanism of apoptosis induction by inhibition of the antiapoptotic BCL-2 proteins. Proc. Natl. Acad. Sci. USA. 105 (2008) 20327- 20332.
• 91. Chen, L., Willis, S.N., Wei, A., Smith, B.J., Fletcher, J.I., Hinds, M.G., Colman, P.M., Day, C.L., Adams, J.M. and Huang, D.C. Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol. Cell 17 (2005) 393-403.
• 92. Vaseva, A.V. and Moll, U.M. The mitochondrial p53 pathway. Biochim. Biophys. Acta 1787 (2009) 414-420.
• 93. Vousden, K.H. Apoptosis – p53 and PUMA: a deadly duo. Science 309 (2005) 1685-1686.
• 94. Chipuk, J.E., Bouchier-Haues, L., Kuwana, T., Newmeyer, D.D. and Green D.R. PUMA couples the nuclear and cytoplasmic proapoptotic function of p53. Science 309 (2005) 1732-1735.
• 95. Wolff, S., Erster, S., Palacios, G. and Moll, U.M. p53’s mitochondrial translocation and MOMP action is independent of Puma and Bax and severaly disrupts mitochondrial membrane integrity. Cell Res. 18 (2008) 733-744.
• 96. Yoo, N.J., Lee, J.W., Jeong, E.G. and Lee, S.H. Immunohistochemical analysis of pro-apoptotic PUMA protein and mutational analysis of PUMA gene in gastric carcinomas. Dig. Liver Dis. 39 (2007) 222-227.
• 97. Kuroda J. and Taniwaki, M. Involvement of BH3-only proteins in hematologic malignancies. Crit. Rev. Oncol. Hematol. 71 (2009) 89-101.
• 98. Pietsch, E.C., Sykes, S.M., McMahon, S.B. and Murphy, M.E. The p53 family and programmed cell death. Oncogene 27 (2008) 6507-6521.
• 99. Hoque, M.O., Begum, S., Sommer, M., Lee, T., Trink, B., Ratovitski, E. and Sidransky, D. PUMA in head and neck cancer. Cancer Lett. 199 (2003) 75-81.
• 100. Ahn, C.H., Jeong, E.G., Kim, S.S., Lee, J.W., Lee, S.H., Kim, S.H., Kim, M.S., Yoo, N.J. and Lee, S.H. Expressional and mutational analysis of proapoptotic Bcl-2 member PUMA in hepatocellular carcinomas. Dig. Dis. Sci. 53 (2008) 1395-1399.
• 101. Kim, M.R, Jeong, E.G., Chae, B., Lee, J.W., Soung, Y.H., Nam, S.W., Lee, J.Y., Yoo, N.J. and Sug H Lee. Pro-apoptotic PUMA and antiapoptotic phospho-BAD are highly expressed in colorectal carcinomas. Dig. Dis. Sci. 52 (2007) 2751-2756.
• 102. Michalak, E.M., Jansen, E.S., Happo, L., Cragg, M.S., Tai, L., Smyth, G.K., Strasser, A., Adams, J.M. and Scott, C.L. Puma and to a lesser extent Noxa are suppressors of Myc-induced lymphomagenesis. Cell Death Differ. 16 (2009).
• 103. Sharma, A.D., Narain, N., Händel, E-M., Iken, M., Singhal, N., Cathomen, T., Manns, M.P., Schöler, H.R., Ott, M. and Cantz, T. MicroRNA-221 regulates FAS-induced fulminant liver failure. Hepatology 53 (2011) 1651-1661.
• 104. Shao, L., Sun, Y., Zhang, Z., Feng, W., Gao, Y., Cai, Z., Wang, Z.Z., Look, A.T. and Wu, W.S. Deletion of proapototic Puma selectively protects hematopoietic stem and progenitor cells against high dose radiation. Blood 115 (2010) 4707-4714.
• 105. Yu, H., Shen, H., Yuan, Y., Xu-Feng, R., Hu, X., Garrison, S.P., Zhang, L., Yu, J., Zambetti, G.P. and Cheng, T. Deletion of Puma protects hematopoietic stem cells and confers long term survival in response to high-dose radiation. Blood 115 (2010) 3472-3480.
• 106. Labi, V., Erlacher, M., Krumschnabel, G., Manzl, C., Tzankov, A., Pinon, J., Egle, A. and Villunger, A. Apoptosis of leukocytes triggered by acute DNA damage promotes lymphoma formation. Genes Dev. 25 (2010) 1602- 1607.
• 107. Michalak, E.M., Vandenberg, C.J., Delbridge, A.R.D., Wu, L., Scott, C.L., Adams, J.M. and Strasser, A. Apoptosis-promoted tumorgenesis: γ-irradiation-induced thymic lymphpomagenesis requires Puma-driven leukocyte death. Genes Dev. 24 (2010) 1608-1613.
• 108. Qiu, W., Wang, X., Leibowitz, B., Yang, W., Zhang, L. and Yu, J. PUMAmediated apoptosis drives chemical hepatocarcinogenesis in mice. Hepatology 54 (2011) 1249-1258.
• 109. Llambi, F. and Green, D.R. Apoptosis and oncogenesis: give and take in the BLC-2 family. Curr. Opin. Genet. Dev. 21 (2011) 12-20.
• 110. Li, F., Huang, Q., Chen, J., Peng, Y., Roop, D., Bedford, J.S. and Li, C-Y. Apoptotic cells activate the “phoenix rising” pathway to promote wound healing and tissue regeneration. Sci. Signal. 3 (2010) 10.1126/scisignal.2000634.
• 111. Baumgartner, F., Villunger, A. Apoptosis: a barrier against cancer no more? Hepatology 54 (2011) 1121-1124.
• 112. Labi, V. and Villunger, A. PUMA-mediated tumor suppression. Cell cycle 9 (2010) 4269-4275.