Tumor suppressors: Enhancers or suppressors of regeneration?

Development (Cambridge)

Volumn 140, Issue 12, 2013, Pages 2502-2512

  Pomerantz, Jason H ^a,b,c   Blau, Helen M ^d,e  

^a Department of Surgery   (United States)

^b Department of Orofacial Sciences ^*

^c UNIVERSITY OF CALIFORNIA   (United States)

^d STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e STANFORD UNIVERSITY   (United States)

Author keywords

Differentiation; Evolution; Regeneration; Tissue homeostasis; Tumor suppressors

Indexed keywords

HIPPO PROTEIN; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN P53; PROTEIN PRB1; TUMOR SUPPRESSOR PROTEIN; UNCLASSIFIED DRUG;

ARTICLE; CANCER INHIBITION; CELL FUNCTION; HUMAN; NONHUMAN; PRIORITY JOURNAL; REGENERATIVE MEDICINE; TISSUE REGENERATION; TUMOR SUPPRESSOR GENE; VERTEBRATE;

DIFFERENTIATION; EVOLUTION; REGENERATION; TISSUE HOMEOSTASIS; TUMOR SUPPRESSORS;

ANIMALS; APOPTOSIS; CELL DIFFERENTIATION; CELL PROLIFERATION; CYCLIN-DEPENDENT KINASE INHIBITOR P16; DISEASE SUSCEPTIBILITY; DROSOPHILA; DROSOPHILA PROTEINS; GENE EXPRESSION REGULATION, NEOPLASTIC; GENES, TUMOR SUPPRESSOR; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MICE; MUTATION; NEOPLASMS; PROTEIN-SERINE-THREONINE KINASES; PTEN PHOSPHOHYDROLASE; REGENERATION; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR PROTEIN P53;

MAMMALIA;

EID: 84878326006     PISSN: 09501991     EISSN: 14779129     Source Type: Journal    
DOI: 10.1242/dev.084210     Document Type: Article

References (115)

1. Amatruda, J. F., Shepard, J. L., Stern, H. M. and Zon, L. I. (2002). Zebrafish as a cancer model system. Cancer Cell 1, 229-231.
2. Anver, M. R. (1992). Amphibian tumors: a comparison of anurans and urodeles. In Vivo 6, 435-437.
3. Armstrong, J. F., Kaufman, M. H., Harrison, D. J. and Clarke, A. R. (1995). High-frequency developmental abnormalities in p53-deficient mice. Curr. Biol. 5, 931-936.
4. Arthur, L. M., Demarest, R. M., Clark, L., Gourevitch, D., Bedelbaeva, K., Anderson, R., Snyder, A., Capobianco, A. J., Lieberman, P., Feigenbaum, L. et al. (2010). Epimorphic regeneration in mice is p53-independent. Cell Cycle 9, 3667-3673.
5. Basu, S., Totty, N. F., Irwin, M. S., Sudol, M. and Downward, J. (2003). Akt phosphorylates the Yes-associated protein, YAP, to induce interaction with 14-3-3 and attenuation of p73-mediated apoptosis. Mol. Cell 11, 11-23.
6. Bedelbaeva, K., Snyder, A., Gourevitch, D., Clark, L., Zhang, X. M., Leferovich, J., Cheverud, J. M., Lieberman, P. and Heber-Katz, E. (2010). Lack of p21 expression links cell cycle control and appendage regeneration in mice. Proc. Natl. Acad. Sci. USA 107, 5845-5850.
7. Belyi, V. A., Ak, P., Markert, E., Wang, H., Hu, W., Puzio-Kuter, A. and Levine, A. J. (2010). The origins and evolution of the p53 family of genes. Cold Spring Harb. Perspect. Biol. 2, a001198.
8. Ben-Porath, I. and Weinberg, R. A. (2005). The signals and pathways activating cellular senescence. Int. J. Biochem. Cell Biol. 37, 961-976.
9. Blau, H. M. and Pomerantz, J. H. (2011). Re"evolutionary" regenerative medicine. JAMA 305, 87-88.
10. Braun, A. C. (1965). The reversal of tumor growth. Sci. Am. 213, 75-83.
11. Breedis, C. (1952). Induction of accessory limbs and of sarcoma in the Newt (Triturus viridescens) with carcinogenic substances. Cancer Res. 12, 861-866.
12. Brockes, J. P. (1998). Regeneration and cancer. Biochim. Biophys. Acta 1377, M1-M11.
13. Brockes, J. P. and Kumar, A. (2008). Comparative aspects of animal regeneration. Annu. Rev. Cell Dev. Biol. 24, 525-549.
14. Burkhart, D. L. and Sage, J. (2008). Cellular mechanisms of tumour suppression by the retinoblastoma gene. Nat. Rev. Cancer 8, 671-682.
15. Campisi, J. and d'Adda di Fagagna, F. (2007). Cellular senescence: when bad things happen to good cells. Nat. Rev. Mol. Cell Biol. 8, 729-740.
16. Cavenee, W. K., Dryja, T. P., Phillips, R. A., Benedict, W. F., Godbout, R., Gallie, B. L., Murphree, A. L., Strong, L. C. and White, R. L. (1983). Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature 305, 779-784.
17. Cid, V. J., Rodríguez-Escudero, I., Andrés-Pons, A., Romá-Mateo, C., Gil, A., den Hertog, J., Molina, M. and Pulido, R. (2008). Assessment of PTEN tumor suppressor activity in nonmammalian models: the year of the yeast. Oncogene 27, 5431-5442.
18. Clarke, A. R., Maandag, E. R., van Roon, M., van der Lugt, N. M., van der Valk, M., Hooper, M. L., Berns, A. and te Riele, H. (1992). Requirement for a functional Rb-1 gene in murine development. Nature 359, 328-330.
19. Croushore, J. A., Blasiole, B., Riddle, R. C., Thisse, C., Thisse, B., Canfield, V. A., Robertson, G. P., Cheng, K. C. and Levenson, R. (2005). Ptena and ptenb genes play distinct roles in zebrafish embryogenesis. Dev. Dyn. 234, 911-921.
20. del Arroyo, A. G. and Peters, G. (2005). The Ink4a/Arf network-cell cycle checkpoint or emergency brake? Adv. Exp. Med. Biol. 570, 227-247.
21. Di Cristofano, A., Pesce, B., Cordon-Cardo, C. and Pandolfi, P. P. (1998). Pten is essential for embryonic development and tumour suppression. Nat. Genet. 19, 348-355.
22. Di Giovanni, S., Knights, C. D., Rao, M., Yakovlev, A., Beers, J., Catania, J., Avantaggiati, M. L. and Faden, A. I. (2006). The tumor suppressor protein p53 is required for neurite outgrowth and axon regeneration. EMBO J. 25, 4084-4096.
23. Donehower, L. A., Harvey, M., Slagle, B. L., McArthur, M. J., Montgomery, C. A., Jr, Butel, J. S. and Bradley, A. (1992). Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 356, 215-221.
24. Dötsch, V., Bernassola, F., Coutandin, D., Candi, E. and Melino, G. (2010). p63 and p73, the ancestors of p53. Cold Spring Harb. Perspect. Biol. 2, a004887.
25. Ewen, M. E., Xing, Y. G., Lawrence, J. B. and Livingston, D. M. (1991). Molecular cloning, chromosomal mapping, and expression of the cDNA for p107, a retinoblastoma gene product-related protein. Cell 66, 1155-1164.
26. Faucherre, A., Taylor, G. S., Overvoorde, J., Dixon, J. E. and Hertog, J. (2008). Zebrafish pten genes have overlapping and non-redundant functions in tumorigenesis and embryonic development. Oncogene 27, 1079-1086.
27. Ferretti, P. and Brockes, J. P. (1988). Culture of newt cells from different tissues and their expression of a regeneration-associated antigen. J. Exp. Zool. 247, 77-91.
28. Friend, S. H., Bernards, R., Rogelj, S., Weinberg, R. A., Rapaport, J. M., Albert, D. M. and Dryja, T. P. (1986). A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 323, 643-646.
29. Gilley, J. and Fried, M. (2001). One INK4 gene and no ARF at the Fugu equivalent of the human INK4A/ARF/INK4B tumour suppressor locus. Oncogene 20, 7447-7452.
30. Gottlieb, E. and Vousden, K. H. (2010). p53 regulation of metabolic pathways. Cold Spring Harb. Perspect. Biol. 2, a001040.
31. Greaves, M. (2007). Darwinian medicine: a case for cancer. Nat. Rev. Cancer 7, 213-221.
32. Green, D.E. and Harshbarger, J. C. (2001). Spontaneous neoplasia in amphibia. In Amphibian Medicine and Captive Husbandry (ed. K. M. Wright and B. R. Whitaker), pp. 335-400.
33. Malabar, FL: Krieger Publishing Gressner, O., Schilling, T., Lorenz, K., Schulze Schleithoff, E., Koch, A., Schulze-Bergkamen, H., Lena, A. M., Candi, E., Terrinoni, A., Catani, M. V. et al. (2005). TAp63alpha induces apoptosis by activating signaling via death receptors and mitochondria. EMBO J. 24, 2458-2471.
34. Gu, W., Schneider, J. W., Condorelli, G., Kaushal, S., Mahdavi, V. and Nadal-Ginard, B. (1993). Interaction of myogenic factors and the retinoblastoma protein mediates muscle cell commitment and differentiation. Cell 72, 309-324.
35. Gyda, M., Wolman, M., Lorent, K. and Granato, M. (2012). The tumor suppressor gene retinoblastoma-1 is required for retinotectal development and visual function in zebrafish. PLoS Genet. 8, e1003106.
36. Hannon, G. J., Demetrick, D. and Beach, D. (1993). Isolation of the Rb-related p130 through its interaction with CDK2 and cyclins. Genes Dev. 7 12A, 2378-2391.
37. Hernández-Martínez, R. and Covarrubias, L. (2011). Interdigital cell death function and regulation: new insights on an old programmed cell death model. Dev. Growth Differ. 53, 245-258.
38. Hong, H., Takahashi, K., Ichisaka, T., Aoi, T., Kanagawa, O., Nakagawa, M., Okita, K. and Yamanaka, S. (2009). Suppression of induced pluripotent stem cell generation by the p53-p21 pathway. Nature 460, 1132-1135.
39. Jacks, T., Fazeli, A., Schmitt, E. M., Bronson, R. T., Goodell, M. A. and Weinberg, R. A. (1992). Effects of an Rb mutation in the mouse. Nature 359, 295-300.
40. Janzen, V., Forkert, R., Fleming, H. E., Saito, Y., Waring, M. T., Dombkowski, D. M., Cheng, T., DePinho, R. A., Sharpless, N. E. and Scadden, D. T. (2006). Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature 443, 421-426.
41. Jiang, Q., Liu, D., Gong, Y., Wang, Y., Sun, S., Gui, Y. and Song, H. (2009). yap is required for the development of brain, eyes, and neural crest in zebrafish. Biochem. Biophys. Res. Commun. 384, 114-119.
42. Junttila, M. R. and Evan, G. I. (2009). p53 - a Jack of all trades but master of none. Nat. Rev. Cancer 9, 821-829.
43. Kawamura, T., Suzuki, J., Wang, Y. V., Menendez, S., Morera, L. B., Raya, A., Wahl, G. M. and Izpisúa Belmonte, J. C. (2009). Linking the p53 tumour suppressor pathway to somatic cell reprogramming. Nature 460, 1140-1144.
44. Kim, W. Y. and Sharpless, N. E. (2006). The regulation of INK4/ARF in cancer and aging. Cell 127, 265-275.
45. Kim, S. H., Mitchell, M., Fujii, H., Llanos, S. and Peters, G. (2003). Absence of p16INK4a and truncation of ARF tumor suppressors in chickens. Proc. Natl. Acad. Sci. USA 100, 211-216.
46. Kim, E., Giese, A. and Deppert, W. (2009). Wild-type p53 in cancer cells: when a guardian turns into a blackguard. Biochem. Pharmacol. 77, 11-20.
47. Kishi, S., Uchiyama, J., Baughman, A. M., Goto, T., Lin, M. C. and Tsai, S. B. (2003). The zebrafish as a vertebrate model of functional aging and very gradual senescence. Exp. Gerontol. 38, 777-786.
48. Knudson, A. G., Jr (1971). Mutation and cancer: statistical study of retinoblastoma. Proc. Natl. Acad. Sci. USA 68, 820-823.
49. Kondo, S. (1998). Apoptotic repair of genotoxic tissue damage and the role of p53 gene. Mutat. Res. 402, 311-319.
50. Koster, M. I., Kim, S., Mills, A. A., DeMayo, F. J. and Roop, D. R. (2004). p63 is the molecular switch for initiation of an epithelial stratification program. Genes Dev. 18, 126-131.
51. Krishnamurthy, J., Ramsey, M. R., Ligon, K. L., Torrice, C., Koh, A., Bonner-Weir, S. and Sharpless, N. E. (2006). p16INK4a induces an age-dependent decline in islet regenerative potential. Nature 443, 453-457.
52. Langheinrich, U., Hennen, E., Stott, G. and Vacun, G. (2002). Zebrafish as a model organism for the identification and characterization of drugs and genes affecting p53 signaling. Curr. Biol. 12, 2023-2028.
53. Lassar, A. and Münsterberg, A. (1994). Wiring diagrams: regulatory circuits and the control of skeletal myogenesis. Curr. Opin. Cell Biol. 6, 432-442.
54. Lee, E. Y., Chang, C. Y., Hu, N., Wang, Y. C., Lai, C. C., Herrup, K., Lee, W. H. and Bradley, A. (1992). Mice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesis. Nature 359, 288-294.
55. Lee, J. O., Russo, A. A. and Pavletich, N. P. (1998). Structure of the retinoblastoma tumour-suppressor pocket domain bound to a peptide from HPV E7. Nature 391, 859-865.
56. Lehman, J. A., Waning, D. L., Batuello, C. N., Cipriano, R., Kadakia, M. P. and Mayo, L. D. (2011). Induction of apoptotic genes by a p73-phosphatase and tensin homolog (p73-PTEN) protein complex in response to genotoxic stress. J. Biol. Chem. 286, 36631-36640.
57. Li, Y., Graham, C., Lacy, S., Duncan, A. M. and Whyte, P. (1993). The adenovirus E1A-associated 130-kD protein is encoded by a member of the retinoblastoma gene family and physically interacts with cyclins A and E. Genes Dev. 7 12A, 2366-2377.
58. Li, J., Yen, C., Liaw, D., Podsypanina, K., Bose, S., Wang, S. I., Puc, J., Miliaresis, C., Rodgers, L., McCombie, R. et al. (1997). PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275, 1943-1947.
59. Li, H., Collado, M., Villasante, A., Strati, K., Ortega, S., Cañamero, M., Blasco, M. A. and Serrano, M. (2009). The Ink4/Arf locus is a barrier for iPS cell reprogramming. Nature 460, 1136-1139.
60. Lindsten, T., Ross, A. J., King, A., Zong, W. X., Rathmell, J. C., Shiels, H. A., Ulrich, E., Waymire, K. G., Mahar, P., Frauwirth, K. et al. (2000). The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues. Mol. Cell 6, 1389-1399.
61. Liu, S. and Leach, S. D. (2011). Zebrafish models for cancer. Annu. Rev. Pathol. 6, 71-93.
62. Liu, K., Lu, Y., Lee, J. K., Samara, R., Willenberg, R., Sears-Kraxberger, I., Tedeschi, A., Park, K. K., Jin, D., Cai, B. et al. (2010). PTEN deletion enhances the regenerative ability of adult corticospinal neurons. Nat. Neurosci. 13, 1075-1081.
63. Love, N. R., Chen, Y., Ishibashi, S., Kritsiligkou, P., Lea, R., Koh, Y., Gallop, J. L., Dorey, K. and Amaya, E. (2013). Amputation-induced reactive oxygen species are required for successful Xenopus tadpole tail regeneration. Nat. Cell Biol. 15, 222-228.
64. Lu, W. J. and Abrams, J. M. (2006). Lessons from p53 in non-mammalian models. Cell Death Differ. 13, 909-912.
65. Malkin, D., Li, F. P., Strong, L. C., Fraumeni, J. F., Jr, Nelson, C. E., Kim, D. H., Kassel, J., Gryka, M. A., Bischoff, F. Z., Tainsky, M. A. et al. (1990). Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250, 1233-1238.
66. Mariani, F. V. (2010). Proximal to distal patterning during limb development and regeneration: a review of converging disciplines. Regen. Med. 5, 451-462.
67. Marión, R. M., Strati, K., Li, H., Murga, M., Blanco, R., Ortega, S., Fernandez-Capetillo, O., Serrano, M. and Blasco, M. A. (2009). A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity. Nature 460, 1149-1153.
68. Menendez, S., Camus, S., Herreria, A., Paramonov, I., Morera, L. B., Collado, M., Pekarik, V., Maceda, I., Edel, M., Consiglio, A. et al. (2012). Increased dosage of tumor suppressors limits the tumorigenicity of iPS cells without affecting their pluripotency. Aging Cell 11, 41-50.
69. Nacu, E. and Tanaka, E. M. (2011). Limb regeneration: a new development? Annu. Rev. Cell Dev. Biol. 27, 409-440.
70. Nejigane, S., Haramoto, Y., Okuno, M., Takahashi, S. and Asashima, M. (2011). The transcriptional coactivators Yap and TAZ are expressed during early Xenopus development. Int. J. Dev. Biol. 55, 121-126.
71. Newmark, P. A. and Sánchez Alvarado, A. (2000). Bromodeoxyuridine specifically labels the regenerative stem cells of planarians. Dev. Biol. 220, 142-153.
72. Newmark, P. A. and Sánchez Alvarado, A. (2002). Not your father's planarian: a classic model enters the era of functional genomics. Nat. Rev. Genet. 3, 210-219.
73. Novitch, B. G., Mulligan, G. J., Jacks, T. and Lassar, A. B. (1996). Skeletal muscle cells lacking the retinoblastoma protein display defects in muscle gene expression and accumulate in S and G2 phases of the cell cycle. J. Cell Biol. 135, 441-456.
74. Okamoto, M. (1997). Simultaneous demonstration of lens regeneration from dorsal iris and tumour production from ventral iris in the same newt eye after carcinogen administration. Differentiation 61, 285-292.
75. Oviedo, N. J. and Beane, W. S. (2009). Regeneration: The origin of cancer or a possible cure? Semin. Cell Dev. Biol. 20, 557-564.
76. Oviedo, N. J., Pearson, B. J., Levin, M. and Sánchez Alvarado, A. (2008). Planarian PTEN homologs regulate stem cells and regeneration through TOR signaling. Dis. Model. Mech. 1, 131-143, discussion 141.
77. Pajcini, K. V., Corbel, S. Y., Sage, J., Pomerantz, J. H. and Blau, H. M. (2010). Transient inactivation of Rb and ARF yields regenerative cells from postmitotic mammalian muscle. Cell Stem Cell 7, 198-213.
78. Pan, D. (2010). The hippo signaling pathway in development and cancer. Dev. Cell 19, 491-505.
79. Pardali, K., Kurisaki, A., Morén, A., ten Dijke, P., Kardassis, D. and Moustakas, A. (2000). Role of Smad proteins and transcription factor Sp1 in p21(Waf1/Cip1) regulation by transforming growth factor-beta. J. Biol. Chem. 275, 29244-29256.
80. Park, K. K., Liu, K., Hu, Y., Smith, P. D., Wang, C., Cai, B., Xu, B., Connolly, L., Kramvis, I., Sahin, M. et al. (2008). Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway. Science 322, 963-966.
81. Pearson, B. J. and Sánchez Alvarado, A. (2008). Regeneration, stem cells, and the evolution of tumor suppression. Cold Spring Harb. Symp. Quant. Biol. 73, 565-572.
82. Pearson, B. J. and Sánchez Alvarado, A. (2010). A planarian p53 homolog regulates proliferation and self-renewal in adult stem cell lineages. Development 137, 213-221.
83. Pfeiffer, C. J., Nagai, T., Fujimura, M. and Tobe, T. (1985). Teratogenic effects of carcinogenic agents on limb regeneration in the Japanese newt Cynops pyrrhogaster. Teratog. Carcinog. Mutagen. 5, 137-147.
84. Quelle, D. E., Zindy, F., Ashmun, R. A. and Sherr, C. J. (1995). Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest. Cell 83, 993-1000.
85. Reddien, P. W. and Sánchez Alvarado, A. (2004). Fundamentals of planarian regeneration. Annu. Rev. Cell Dev. Biol. 20, 725-757.
86. Ren, D., Tu, H. C., Kim, H., Wang, G. X., Bean, G. R., Takeuchi, O., Jeffers, J. R., Zambetti, G. P., Hsieh, J. J. and Cheng, E. H. (2010). BID, BIM, and PUMA are essential for activation of the BAX-and BAK-dependent cell death program. Science 330, 1390-1393.
87. Ríos, Y., Melmed, S., Lin, S. and Liu, N. A. (2011). Zebrafish usp39 mutation leads to rb1 mRNA splicing defect and pituitary lineage expansion. PLoS Genet. 7, e1001271.
88. Seifert, A. W. and Voss, S. R. (2013). Revisiting the relationship between regenerative ability and aging. BMC Biol. 11, 2.
89. Serrano, M., Lee, H., Chin, L., Cordon-Cardo, C., Beach, D. and DePinho, R. A. (1996). Role of the INK4a locus in tumor suppression and cell mortality. Cell 85, 27-37.
90. Sharpless, N. E. and DePinho, R. A. (2007). How stem cells age and why this makes us grow old. Nat. Rev. Mol. Cell Biol. 8, 703-713.
91. Sherr, C. J. (2004). Principles of tumor suppression. Cell 116, 235-246.
92. Singer, M. (1974). Trophic functions of the neuron. VI. Other trophic systems. Neurotrophic control of limb regeneration in the newt. Ann. N. Y. Acad. Sci. 228, 308-322.
93. Sogame, N., Kim, M. and Abrams, J. M. (2003). Drosophila p53 preserves genomic stability by regulating cell death. Proc. Natl. Acad. Sci. USA 100, 4696-4701.
94. Spitsbergen, J. M., Buhler, D. R. and Peterson, T. S. (2012). Neoplasia and neoplasm-associated lesions in laboratory colonies of zebrafish emphasizing key influences of diet and aquaculture system design. ILAR J. 53, 114-125.
95. Steck, P. A., Pershouse, M. A., Jasser, S. A., Yung, W. K., Lin, H., Ligon, A. H., Langford, L. A., Baumgard, M. L., Hattier, T., Davis, T. et al. (1997). Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat. Genet. 15, 356-362.
96. Suh, E. K., Yang, A., Kettenbach, A., Bamberger, C., Michaelis, A. H., Zhu, Z., Elvin, J. A., Bronson, R. T., Crum, C. P. and McKeon, F. (2006). p63 protects the female germ line during meiotic arrest. Nature 444, 624-628.
97. Sun, H., Lesche, R., Li, D. M., Liliental, J., Zhang, H., Gao, J., Gavrilova, N., Mueller, B., Liu, X. and Wu, H. (1999). PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B signaling pathway. Proc. Natl. Acad. Sci. USA 96, 6199-6204.
98. Sun, F., Park, K. K., Belin, S., Wang, D., Lu, T., Chen, G., Zhang, K., Yeung, C., Feng, G., Yankner, B. A. et al. (2011). Sustained axon regeneration induced by co-deletion of PTEN and SOCS3. Nature 480, 372-375.
99. Tanaka, E. M., Gann, A. A., Gates, P. B. and Brockes, J. P. (1997). Newt myotubes reenter the cell cycle by phosphorylation of the retinoblastoma protein. J. Cell Biol. 136, 155-165.
100. Thitoff, A. R., Call, M. K., Del Rio-Tsonis, K. and Tsonis, P. A. (2003). Unique expression patterns of the retinoblastoma (Rb) gene in intact and lens regeneration-undergoing newt eyes. Anat. Rec. A Discov. Mol. Cell. Evol. Biol. 271, 185-188.
101. Thom, S. R. (2009). Oxidative stress is fundamental to hyperbaric oxygen therapy. J. Appl. Physiol. 106, 988-995.
102. Tomasini, R., Tsuchihara, K., Wilhelm, M., Fujitani, M., Rufini, A., Cheung, C. C., Khan, F., Itie-Youten, A., Wakeham, A., Tsao, M. S. et al. (2008). TAp73 knockout shows genomic instability with infertility and tumor suppressor functions. Genes Dev. 22, 2677-2691.
103. Trabold, O., Wagner, S., Wicke, C., Scheuenstuhl, H., Hussain, M. Z., Rosen, N., Seremetiev, A., Becker, H. D. and Hunt, T. K. (2003). Lactate and oxygen constitute a fundamental regulatory mechanism in wound healing. Wound Repair Regen. 11, 504-509.
104. Tsonis, P. A. (1983). Effects of carcinogens on regenerating and nonregenerating limbs in amphibia (review). Anticancer Res. 3, 195-202.
105. Tsonis, P. A. and Eguchi, G. (1981). Carcinogens on regeneration. Effects of Nmethyl-N'-nitro-N-nitrosoguanidine and 4-nitroquinoline-1-oxide on limb regeneration in adult newts. Differentiation 20, 52-60.
106. Utikal, J., Polo, J. M., Stadtfeld, M., Maherali, N., Kulalert, W., Walsh, R. M., Khalil, A., Rheinwald, J. G. and Hochedlinger, K. (2009). Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature 460, 1145-1148.
107. Villiard, E., Brinkmann, H., Moiseeva, O., Mallette, F. A., Ferbeyre, G. and Roy, S. (2007). Urodele p53 tolerates amino acid changes found in p53 variants linked to human cancer. BMC Evol. Biol. 7, 180.
108. Vousden, K. H. and Prives, C. (2009). Blinded by the Light: The Growing Complexity of p53. Cell 137, 413-431.
109. Wells, B. S., Yoshida, E. and Johnston, L. A. (2006). Compensatory proliferation in Drosophila imaginal discs requires Dronc-dependent p53 activity. Curr. Biol. 16, 1606-1615.
110. Worley, M. I., Setiawan, L. and Hariharan, I. K. (2012). Regeneration and transdetermination in Drosophila imaginal discs. Annu. Rev. Genet. 46, 289-310.
111. Wright, K. M. and Whitaker, B. R. (2001) Amphibian Medicine and Captive Husbandry. Malabar, FL: Krieger Publishing.
112. Wu, S., Huang, J., Dong, J. and Pan, D. (2003). hippo encodes a Ste-20 family protein kinase that restricts cell proliferation and promotes apoptosis in conjunction with salvador and warts. Cell 114, 445-456.
113. Zhao, B., Tumaneng, K. and Guan, K. L. (2011). The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal. Nat. Cell Biol. 13, 877-883.
114. Zilakos, N. P., Zafiratos, C. S. and Parchment, R. E. (1996). Stage-dependent genetically-based deformities of the regenerating newt limb from 4-nitroquinoline-N-oxide mutagenesis: potential embryonic regulation of cancer. Differentiation 60, 67-74.
115. Zuzarte-Luis, V. and Hurle, J. M. (2005). Programmed cell death in the embryonic vertebrate limb. Semin. Cell Dev. Biol. 16, 261-269.