Autophagy, apoptosis, mitoptosis and necrosis: Interdependence between those pathways and effects on cancer

Archivum Immunologiae et Therapiae Experimentalis

Volumn 61, Issue 1, 2013, Pages 43-58

  Chaabane, Wiem ^a,b   User, Sirma D ^a,c   El Gazzah, Mohamed ^b   Jaksik, Roman ^d   Sajjadi, Elaheh ^e   Rzeszowska Wolny, Joanna ^d   Łos, Marek J ^a,f  

^a LINKÖPING UNIVERSITY   (Sweden)

^b UNIVERSITY OF TUNIS   (Tunisia)

^c MIDDLE EAST TECHNICAL UNIVERSITY   (Turkey)

^d SILESIAN UNIVERSITY OF TECHNOLOGY   (Poland)

^e TEHRAN UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^f BioApplications Enterprises Winnipeg   (Canada)

Author keywords

AMPK; Hsp 70; Mdm2; Mitochondria; mTOR; PARP 1; PKC delta; RIPK; TNF; VHL

Indexed keywords

ALKYLATING AGENT; ANTINEOPLASTIC AGENT; BEVACIZUMAB; BORTEZOMIB; CAPECITABINE; CARBOPLATIN; CASPASE; CHLOROQUINE; CONTUSUGENE LADENOVEC; DEOXYGLUCOSE; DOCETAXEL; DOXORUBICIN; GENDICINE; HYDROXYCHLOROQUINE; IXABEPILONE; METFORMIN; N (3 METHYLPHENYL) 4 (4 PYRIDINYL) 2 THIAZOLAMINE; NUTLIN 3; OXALIPLATIN; PACLITAXEL; PHENYLETHYNESULFONAMIDE; PROTEIN BCL XL; PROTEIN P53; PROTEIN RIPK1; PROTEIN RIPK3; PROTEIN SERINE THREONINE KINASE; TAMOXIFEN; TEMSIROLIMUS; UNCLASSIFIED DRUG; UNINDEXED DRUG; VORINOSTAT;

APOPTOSIS; AUTOPHAGY; BINDING AFFINITY; BINDING SITE; BREAST CANCER; BREAST CARCINOMA; CANCER RADIOTHERAPY; CANCER THERAPY; CELL CYCLE G2 PHASE; CELL CYCLE M PHASE; CELL FUNCTION; CELL STRESS; CELL SURVIVAL; COLORECTAL CANCER; DNA BINDING; DNA DAMAGE; DNA REPAIR; DRUG EFFICACY; DRUG TARGETING; ENZYME ACTIVITY; GENE; GENE TARGETING; HEAD AND NECK CANCER; HUMAN; LOW DRUG DOSE; LUNG CANCER; LUNG NON SMALL CELL CANCER; LYMPHATIC LEUKEMIA; MDM2 GENE; MITOCHONDRION; MULTIPLE MYELOMA; NECROPTOSIS; NECROSIS; NEOPLASM; NEUROBLASTOMA; NONHUMAN; PROSTATE CANCER; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; REVIEW; SOLID TUMOR; TRANSCRIPTION REGULATION; TREATMENT RESPONSE;

ANIMALS; APOPTOSIS; AUTOPHAGY; HUMANS; MITOCHONDRIA; NECROSIS; NEOPLASMS; SIGNAL TRANSDUCTION;

EID: 84872606148     PISSN: 0004069X     EISSN: 16614917     Source Type: Journal    
DOI: 10.1007/s00005-012-0205-y     Document Type: Review

References (143)

1. Aita VM, Liang XH, Murty VV et al (1999) Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21. Genomics 59:59-65
2. Akar U, Ozpolat B, Mehta K et al (2007) Tissue transglutaminase inhibits autophagy in pancreatic cancer cells. Mol Cancer Res 5:241-249
3. Akar U, Chaves-Reyez A, Barria M et al (2008) Silencing of Bcl-2 expression by small interfering RNA induces autophagic cell death in MCF-7 breast cancer cells. Autophagy 4:669-679
4. Alavian SM, Ande SR, Coombs KM et al (2011) Virus-triggered autophagy in viral hepatitis - possible novel strategies for drug development. J Viral Hepat 18:821-830
5. Amaravadi RK, Thompson CB (2007) The roles of therapy-induced autophagy and necrosis in cancer treatment. Clin Cancer Res 13:7271-7279
6. Amaravadi RK, Yu D, Lum JJ et al (2007) Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma. J Clin Invest 117:326-336
7. Ande SR, Chen J, Maddika S (2009) The ubiquitin pathway: an emerging drug target in cancer therapy. Eur J Pharmacol 625:199-205
8. Balakrishnan K, Burger JA, Wierda WG et al (2009) AT-101 induces apoptosis in CLL B cells and overcomes stromal cell-mediated Mcl-1 induction and drug resistance. Blood 113:149-153
9. Barak Y, Juven T, Haffner R et al (1993) mdm2 expression is induced by wild type p53 activity. EMBO J 12:461-468
10. Barczyk K, Kreuter M, Pryjma J et al (2005) Serum cytochrome c indicates in vivo apoptosis and can serve as a prognostic marker during cancer therapy. J Int Cancer 116:167-173
11. Ben Sahra I, Laurent K, Giuliano S et al (2010) Targeting cancer cell metabolism: the combination of metformin and 2-deoxyglucose induces p53-dependent apoptosis in prostate cancer cells. Cancer Res 71:2465-2475
12. Budanov AV, Karin M (2008) p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. Cell 134:451-460
13. Cardinal J, Pan P, Dhupar R et al (2009) Cisplatin prevents high mobility group box 1 release and is protective in a murine model of hepatic ischemia/reperfusion injury. Hepatology 50:565-574
14. 2+ overload. Cell Death Differ 13:1675-1685
15. Chang C, Simmons DT, Martin MA et al (1979) Identification and partial characterization of new antigens from simian virus 40-transformed mouse cells. J Virol 31:463-471
16. Chen X, Ko LJ, Jayaraman L et al (1996) p53 levels, functional domains, and DNA damage determine the extent of the apoptotic response of tumor cells. Genes Dev 10:2438-2451
17. Chen K, Luo Z, Tang J et al (2011) A critical role of heat shock cognate protein 70 in Apoptin-induced phosphorylation of Akt. Biochem Biophys Res Commun 409:200-204
18. Cherlonneix L (2008) L'équivocité vive: Une nouvelle représentation du vivant [The vivid equivocity. A new representation of living]. L'Harmattan, Paris. ISBN: 978-2-296-05340-3
19. Chipuk JE, Kuwana T, Bouchier-Hayes L et al (2004) Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science 303:1010-1014
20. Chipuk JE, Bouchier-Hayes L, Kuwana T et al (2005) PUMA couples the nuclear and cytoplasmic proapoptotic function of p53. Science 309:1732-1735
21. Cho Y, Challa S, Chan FK (2011) A RNA interference screen identifies RIP3 as an essential inducer of TNF-induced programmed necrosis. Adv Exp Med Biol 691:589-593
22. Chua BT, Guo K, Li P (2000) Direct cleavage by the calcium-activated protease calpain can lead to inactivation of caspases. J Biol Chem 275:5131-5135
23. Cieslar-Pobuda A, Saenko Y, Rzeszowska-Wolny J (2012) PARP-1 inhibition induces a late increase in the level of reactive oxygen species in cells after ionizing radiation. Mutat Res 732:9-15
24. Clarke AR, Purdie CA, Harrison DJ et al (1993) Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature 362:849-852
25. Crighton D, Wilkinson S, O'Prey J et al (2006) DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. Cell 126:121-134
26. Curtin JF, Cotter TG (2003) Apoptosis: historical perspectives. Essays Biochem 39:1-10
27. Degterev A, Huang Z, Boyce M et al (2005) Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol 1:112-119
28. Degterev A, Hitomi J, Germscheid M et al (2008) Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol 4:313-321
29. DeLeo AB, Jay G, Appella E et al (1979) Detection of a transformation-related antigen in chemically induced sarcomas and other transformed cells of the mouse. Proc Natl Acad Sci USA 76:2420-2424
30. Denecker G, Vercammen D, Steemans M et al (2001) Death receptor-induced apoptotic and necrotic cell death: differential role of caspases and mitochondria. Cell Death Differ 8:829-840
31. Eguchi Y, Shimizu S, Tsujimoto Y (1997) Intracellular ATP levels determine cell death fate by apoptosis or necrosis. Cancer Res 57:1835-1840
32. Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495-516
33. Emi M, Kim R, Tanabe K et al (2005) Targeted therapy against Bcl-2-related proteins in breast cancer cells. Breast Cancer Res 7:R940-R952
34. Esposti DD, Domart MC, Sebagh M et al (2010) Autophagy is induced by ischemic preconditioning in human livers formerly treated by chemotherapy to limit necrosis. Autophagy 6:172-174
35. Feng Z, Zhang H, Levine AJ et al (2005) The coordinate regulation of the p53 and mTOR pathways in cells. Proc Natl Acad Sci USA 102:8204-8209
36. Fujiwara T, Grimm EA, Mukhopadhyay T et al (1993) A retroviral wild-type p53 expression vector penetrates human lung cancer spheroids and inhibits growth by inducing apoptosis. Cancer Res 53:4129-4133
37. Ghavami S, Hashemi M, Ande SR et al (2009) Apoptosis and cancer: mutations within caspase genes. J Med Genet 46:497-510
38. Ghavami S, Eshragi M, Ande SR et al (2010) S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes that involves BNIP3. Cell Res 20:314-331
39. Ghavami S, Mutawe MM, Sharma P et al (2011) Mevalonate cascade regulation of airway mesenchymal cell autophagy and apoptosis: a dual role for p53. PLoS One 6:e16523
40. Gokay O, Kuhner D, Los M et al (2010) An efficient approach for the isolation, identification and evaluation of antimicrobial plant components on an analytical scale, demonstrated by the example of Radix imperatoriae. Anal Bioanal Chem 398:2039-2047
41. Grinkevich VV, Nikulenkov F, Shi Y et al (2009) Ablation of key oncogenic pathways by RITA-reactivated p53 is required for efficient apoptosis. Cancer Cell 15:441-453
42. Gurevich-Panigrahi T, Panigrahi S, Wiechec E et al (2009) Obesity: pathophysiology and clinical management. Curr Med Chem 16:506-521
43. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57-70
44. Hitomi J, Christofferson DE, Ng A et al (2008) Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway. Cell 135:1311-1323
45. Holler N, Zaru R, Micheau O et al (2000) Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol 1:489-495
46. Holmes T (1856) St. George's Hospital: case of necrosis of the ulna following diffuse inflammation after injury (and probably simple fracture): removal of a sequestrum involving the whole shaft of the bone for seven inches of its length. Assoc Med J 4:1029
47. Hori T, Kondo T, Kanamori M et al (2010) Nutlin-3 enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through up-regulation of death receptor 5 (DR5) in human sarcoma HOS cells and human colon cancer HCT116 cells. Cancer Lett 287:98-108
48. Jangamreddy JR, Los MJ (2012) Mitoptosis, a novel mitochondrial death mechanism leading predominantly to activation of autophagy. Hepat Mon 12:e6159
49. Jeffers JR, Parganas E, Lee Y et al (2003) Puma is an essential mediator of p53-dependent and -independent apoptotic pathways. Cancer Cell 4:321-328
50. Kang MH, Reynolds CP (2009) Bcl-2 inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy. Clin Cancer Res 15:1126-1132
51. 2+ stimulation. Arch Biochem Biophys 482:66-76
52. Kastan MB, Onyekwere O, Sidransky D et al (1991) Participation of p53 protein in the cellular response to DNA damage. Cancer Res 51:6304-6311
53. Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239-257
54. Kinnally KW, Peixoto PM, Ryu SY et al (2011) Is mPTP the gatekeeper for necrosis, apoptosis, or both? Biochim Biophys Acta 1813:616-622
55. Koneri K, Goi T, Hirono Y et al (2007) Beclin 1 gene inhibits tumor growth in colon cancer cell lines. Anticancer Res 27:1453-1457
56. Konopleva M, Watt J, Contractor R et al (2008) Mechanisms of antileukemic activity of the novel Bcl-2 homology domain-3 mimetic GX15-070 (obatoclax). Cancer Res 68:3413-3420
57. Krajewski S, Krajewska M, Turner BC et al (1999) Prognostic significance of apoptosis regulators in breast cancer. Endocr Relat Cancer 6:29-40
58. Kress M, May E, Cassingena R et al (1979) Simian virus 40-transformed cells express new species of proteins precipitable by anti-simian virus 40 tumor serum. J Virol 31:472-483
59. Lane DP, Crawford LV (1979) T antigen is bound to a host protein in SV40-transformed cells. Nature 278:261-263
60. Lee WK, Abouhamed M, Thevenod F (2006) Caspase-dependent and -independent pathways for cadmium-induced apoptosis in cultured kidney proximal tubule cells. Am J Physiol Renal Physiol 291:F823-F832
61. Lee JH, Budanov AV, Park EJ et al (2010) Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies. Science 327:1223-1228
62. Leist M, Jaattela M (2001) Four deaths and a funeral: from caspases to alternative mechanisms. Nat Rev Mol Cell Biol 2:589-598
63. Leu JI, Dumont P, Hafey M et al (2004) Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex. Nat Cell Biol 6:443-450
64. Leu JI, Pimkina J, Frank A et al (2009) A small molecule inhibitor of inducible heat shock protein 70. Mol Cell 36:15-27
65. Levine AJ (1997) p53, the cellular gatekeeper for growth and division. Cell 88:323-331
66. Los M (2009) New, exciting developments in experimental therapies in the early 21st century. Eur J Pharmacol 625:1-5
67. Los M, Wesselborg S, Schulze-Osthoff K (1999) The role of caspases in development, immunity, and apoptotic signal transduction: lessons from knockout mice. Immunity 10:629-639
68. Los M, Stroh C, Janicke RU et al (2001) Caspases: more than just killers? Trends Immunol 22:31-34
69. Los M, Mozoluk M, Ferrari D et al (2002) Activation and caspase-mediated inhibition of PARP: a molecular switch between fibroblast necrosis and apoptosis in death receptor signaling. Mol Biol Cell 13:978-988
70. Los M, Burek CJ, Stroh C et al (2003) Anticancer drugs of tomorrow: apoptotic pathways as targets for drug design. Drug Discov Today 8:67-77
71. Los M, Maddika S, Erb B et al (2009a) Switching Akt: from survival signaling to deadly response. BioEssays 31:492-495
72. Los M, Panigrahi S, Rashedi I et al (2009b) Apoptin, a tumor-selective killer. Biochim Biophys Acta 1793:1335-1342
73. Lowe SW, Ruley HE (1993) Stabilization of the p53 tumor suppressor is induced by adenovirus 5 E1A and accompanies apoptosis. Genes Dev 7:535-545
74. Lowe SW, Schmitt EM, Smith SW et al (1993) p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 362:847-849
75. Lu X, Lane DP (1993) Differential induction of transcriptionally active p53 following UV or ionizing radiation: defects in chromosome instability syndromes? Cell 75:765-778
76. Lu JV, Weist BM, van Raam BJ et al (2011) Complementary roles of Fas-associated death domain (FADD) and receptor interacting protein kinase-3 (RIPK3) in T-cell homeostasis and antiviral immunity. Proc Natl Acad Sci USA 108:15312-15317
77. Lyamzaev KG, Nepryakhina OK, Saprunova VB et al (2008) Novel mechanism of elimination of malfunctioning mitochondria (mitoptosis): formation of mitoptotic bodies and extrusion of mitochondrial material from the cell. Biochim Biophys Acta 1777:817-825
78. Maddika S, Ande SR, Panigrahi S et al (2007) Cell survival, cell death and cell cycle pathways are interconnected: implications for cancer therapy. Drug Resist Updat 10:13-29
79. Maddika S, Ande SR, Wiechec E et al (2008) Akt-mediated phosphorylation of CDK2 regulates its dual role in cell cycle progression and apoptosis. J Cell Sci 121:979-988
80. Maddika S, Panigrahi S, Wiechec E et al (2009) Unscheduled Akt-triggered activation of cyclin-dependent kinase 2 as a key effector mechanism of apoptin's anticancer toxicity. Mol Cell Biol 29:1235-1248
81. Maiuri MC, Malik SA, Morselli E et al (2009) Stimulation of autophagy by the p53 target gene Sestrin2. Cell Cycle 8:1571-1576
82. Martinet W, Schrijvers DM, Herman AG et al (2006) z-VAD-fmk-induced non-apoptotic cell death of macrophages: possibilities and limitations for atherosclerotic plaque stabilization. Autophagy 2:312-314
83. Matthews N (1983) Anti-tumour cytotoxin produced by human monocytes: studies on its mode of action. Br J Cancer 48:405-410
84. McCormick J, Knight RA, Barry SP et al (2012) Autophagy in the stress-induced myocardium. Front Biosci 4:2131-2141
85. Mehrpour M, Esclatine A, Beau I et al (2010) Autophagy in health and disease. 1. Regulation and significance of autophagy: an overview. Am J Physiol Cell Physiol 298:C776-C785
86. Meijer AJ, Codogno P (2009) Autophagy: regulation and role in disease. Crit Rev Clin Lab Sci 46:210-240
87. Mihara M, Erster S, Zaika A et al (2003) p53 has a direct apoptogenic role at the mitochondria. Mol Cell 11:577-590
88. Mijaljica D, Prescott M, Devenish RJ (2010) Mitophagy and mitoptosis in disease processes. Methods Mol Biol 648:93-106
89. Miyashita T, Reed JC (1995) Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80:293-299
90. Mizushima N, Komatsu M (2011) Autophagy: renovation of cells and tissues. Cell 147:728-741
91. Moll UM, Marchenko N, Zhang XK (2006) p53 and Nur77/TR3 - transcription factors that directly target mitochondria for cell death induction. Oncogene 25:4725-4743
92. Momand J, Zambetti GP, Olson DC et al (1992) The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69:1237-1245
93. Moreira JN, Santos A, Simoes S (2006) Bcl-2-targeted antisense therapy (Oblimersen sodium): towards clinical reality. Rev Recent Clin Trials 1:217-235
94. Moroni MC, Hickman ES, Lazzerini Denchi E et al (2001) Apaf-1 is a transcriptional target for E2F and p53. Nat Cell Biol 3:552-558
95. Nakano K, Vousden KH (2001) PUMA, a novel proapoptotic gene, is induced by p53. Mol Cell 7:683-694
96. Nguyen M, Marcellus RC, Roulston A et al (2007) Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis. Proc Natl Acad Sci USA 104:19512-19517
97. Oda E, Ohki R, Murasawa H et al (2000) Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science 288:1053-1058
98. Panigrahi S, Stetefeld J, Jangamreddy JR et al (2012) Modeling of molecular interaction between apoptin, BCR-Abl and CrkL-an alternative approach to conventional rational drug design. PLoS One 7:e28395
99. Paoluzzi L, Gonen M, Gardner JR et al (2008) Targeting Bcl-2 family members with the BH3 mimetic AT-101 markedly enhances the therapeutic effects of chemotherapeutic agents in in vitro and in vivo models of B-cell lymphoma. Blood 111:5350-5358
100. Proskuryakov SY, Konoplyannikov AG, Gabai VL (2003) Necrosis: a specific form of programmed cell death? Exp Cell Res 283:1-16
101. Rikiishi H (2012) Novel insights into the interplay between apoptosis and autophagy. Int J Cell Biol 2012:317645
102. Rom J, von Minckwitz G, Eiermann W et al (2008) Oblimersen combined with docetaxel, adriamycin and cyclophosphamide as neo-adjuvant systemic treatment in primary breast cancer: final results of a multicentric phase I study. Ann Oncol 19:1698-1705
103. Rotter V, Aloni-Grinstein R, Schwartz D et al (1994) Does wild-type p53 play a role in normal cell differentiation? Semin Cancer Biol 5:229-236
104. Ryabokon NI, Goncharova RI, Duburs G et al (2008) Changes in poly(ADP-ribose) level modulate the kinetics of DNA strand break rejoining. Mutat Res 637:173-181
105. Saelens X, Festjens N, Vande Walle L et al (2004) Toxic proteins released from mitochondria in cell death. Oncogene 23:2861-2874
106. Sanli T, Linher-Melville K, Tsakiridis T et al (2012) Sestrin2 modulates AMPK subunit expression and its response to ionizing radiation in breast cancer cells. PLoS One 7:e32035
107. Sax JK, Fei P, Murphy ME et al (2002) BID regulation by p53 contributes to chemosensitivity. Nat Cell Biol 4:842-849
108. Scherz-Shouval R, Weidberg H, Gonen C et al (2010) p53-dependent regulation of autophagy protein LC3 supports cancer cell survival under prolonged starvation. Proc Natl Acad Sci USA 107:18511-18516
109. Schmitt E, Paquet C, Beauchemin M et al (2004) Bcl-xES, a BH4- and BH2-containing antiapoptotic protein, delays Bax oligomer formation and binds Apaf-1, blocking procaspase-9 activation. Oncogene 23:3915-3931
110. Schweichel JU, Merker HJ (1973) The morphology of various types of cell death in prenatal tissues. Teratology 7:253-266
111. Secchiero P, Zerbinati C, Melloni E et al (2007) The MDM-2 antagonist nutlin-3 promotes the maturation of acute myeloid leukemic blasts. Neoplasia 9:853-861
112. Sims JL, Berger SJ, Berger NA (1983) Poly(ADP-ribose) Polymerase inhibitors preserve nicotinamide adenine dinucleotide and adenosine 5′-triphosphate pools in DNA-damaged cells: mechanism of stimulation of unscheduled DNA synthesis. Biochemistry 22:5188-5194
113. Skulachev VP (2006) Bioenergetic aspects of apoptosis, necrosis and mitoptosis. Apoptosis 11:473-485
114. Smith CC, Yellon DM (2011) Necroptosis, necrostatins and tissue injury. J Cell Mol Med 15:1797-1806
115. Sonnemann J, Palani CD, Wittig S et al (2011) Anticancer effects of the p53 activator nutlin-3 in Ewing's sarcoma cells. Eur J Cancer 47:1432-1441
116. Stroh C, Cassens U, Samraj AK et al (2002) The role of caspases in cryoinjury: caspase inhibition strongly improves the recovery of cryopreserved hematopoietic and other cells. FASEB J 16:1651-1653
117. Szabo C, Dawson VL (1998) Role of poly(ADP-ribose) synthetase in inflammation and ischaemia-reperfusion. Trends Pharmacol Sci 19:287-298
118. Tasdemir E, Maiuri MC, Galluzzi L et al (2008a) Regulation of autophagy by cytoplasmic p53. Nat Cell Biol 10:676-687
119. Tasdemir E, Maiuri MC, Orhon I et al (2008b) p53 represses autophagy in a cell cycle-dependent fashion. Cell Cycle 7:3006-3011
120. Thorburn A (2008) Apoptosis and autophagy: regulatory connections between two supposedly different processes. Apoptosis 13:1-9
121. Tomita Y, Marchenko N, Erster S et al (2006) WT p53, but not tumor-derived mutants, bind to Bcl2 via the DNA binding domain and induce mitochondrial permeabilization. J Biol Chem 281:8600-8606
122. Toyota H, Yanase N, Yoshimoto T et al (2003) Calpain-induced Bax-cleavage product is a more potent inducer of apoptotic cell death than wild-type Bax. Cancer Lett 189:221-230
123. Trudel S, Li ZH, Rauw J et al (2007) Preclinical studies of the pan-Bcl inhibitor obatoclax (GX015-070) in multiple myeloma. Blood 109:5430-5438
124. Turcotte S, Chan DA, Sutphin PD et al (2008) A molecule targeting VHL-deficient renal cell carcinoma that induces autophagy. Cancer Cell 14:90-102
125. Van Herreweghe F, Festjens N, Declercq W et al (2010) Tumor necrosis factor-mediated cell death: to break or to burst, that's the question. Cell Mol Life Sci 67:1567-1579
126. Vandenabeele P, Vanden Berghe T, Festjens N (2006) Caspase inhibitors promote alternative cell death pathways. Sci STKE 2006:pe44
127. Vandenabeele P, Declercq W, Van Herreweghe F et al (2010) The role of the kinases RIP1 and RIP3 in TNF-induced necrosis. Sci Signal 3:re4
128. Vincent FC, Los MJ (2011) New potential instrument to fight hepatocellular cancer by restoring p53. Hepat Mon 11:331-332
129. Walsh CM, Edinger AL (2010) The complex interplay between autophagy, apoptosis, and necrotic signals promotes T-cell homeostasis. Immunol Rev 236:95-109
130. Wang Z, Sun Y (2010) Targeting p53 for novel anticancer therapy. Transl Oncol 3:1-12
131. Wiechec E (2011) Implications of genomic instability in the diagnosis and treatment of breast cancer. Expert Rev Mol Diagn 11:445-453
132. Wiechec E, Hansen LL (2009) The effect of genetic variability on drug response in conventional breast cancer treatment. Eur J Pharmacol 625:122-130
133. Wiechec E, Wiuf C, Overgaard J et al (2011) High-resolution melting analysis for mutation screening of RGSL1, RGS16, and RGS8 in breast cancer. Cancer Epidemiol Biomarkers Prev 20:397-407
134. Wu H, Zhu H, Liu DX et al (2009) Silencing of elongation factor-2 kinase potentiates the effect of 2-deoxy-d-glucose against human glioma cells through blunting of autophagy. Cancer Res 69:2453-2460
135. Wyllie AH, Kerr JF, Currie AR (1980) Cell death: the significance of apoptosis. Int Rev Cytol 68:251-306
136. Wynford-Thomas D (1999) Cellular senescence and cancer. J Pathol 187:100-111
137. Xu Y (2003) Regulation of p53 responses by post-translational modifications. Cell Death Differ 10:400-403
138. Xu H, Tai J, Ye H et al (2006) 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 341:938-944
139. Xu H, Ye H, Osman NE et al (2009) The MDM2-binding region in the transactivation domain of p53 also acts as a Bcl-X(L)-binding motif. Biochemistry 48:12159-12168
140. Yu L, Alva A, Su H et al (2004a) Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8. Science 304:1500-1502
141. Yu L, Lenardo MJ, Baehrecke EH (2004b) Autophagy and caspases: a new cell death program. Cell Cycle 3:1124-1126
142. Zhang DW, Shao J, Lin J et al (2009) RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science 325:332-336
143. Zhang F, Tagen M, Throm S et al (2011) Whole-body physiologically based pharmacokinetic model for nutlin-3a in mice after intravenous and oral administration. Drug Metab Dispos 39:15-21