Amati, B., S.R. Frank, et al. (2001). “Function of the c-Myc oncoprotein in chromatin remodeling and transcription.” Biochim Biophys Acta 1471(3): M135-45.
Ashcroft, M., Y. Taya, et al. (2000). “Stress signals utilize multiple pathways to stabilize p53.” Mol Cell Biol 20(9): 3224-33.
Attardi, L.D., A. de Vries, et al. (2004). “Activation of the p53-dependent G1 checkpoint response in mouse embryo fibroblasts depends on the specific DNA damage inducer.” Oncogene 23(4): 973-80.
Bartkova, J., N. Rezaei, et al. (2006). “Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints.” Nature 444(7119): 633-7.
Blackwood, E.M. and R.N. Eisenman (1991). “Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc.” Science 251(4998): 1211-7.
Braithwaite, A.W., G. Del Sal, et al. (2006). “Some p53-binding proteins that can function as arbiters of life and death.” Cell Death Differ 13(6): 984-93.
Brenner, C., R. Deplus, et al. (2005). “Myc represses transcription through recruitment of DNA methyltransferase corepressor.” EMBO J 24(2): 336-46. Brunner, T., S. Kasibhatla, et al. (2000). “Expression of Fas ligand in activated T
cells is regulated by c-Myc.” J Biol Chem 275(13): 9767-72.
Buschges, R., R.G. Weber, et al. (1999). “Amplification and expression of cyclin D genes (CCND1, CCND2 and CCND3) in human malignant gliomas.” Brain Pathol 9(3): 435-42; discussion 432-3.
Campisi, J. and F. d’Adda di Fagagna (2007). “Cellular senescence: when bad things happen to good cells.” Nat Rev Mol Cell Biol 8(9): 729-40.
Caspari, T. (2000). “How to activate p53.” Curr Biol 10(8): R315-7. Cecchinelli, B., A. Porrello, et al. (2006). “Ser58
of mouse p53 is the homologue of human Ser46
and is phosphorylated by HIPK2 in apoptosis.” Cell Death Differ 13(11): 1994-7.
Ciemerych, M.A. and P. Sicinski (2005). “Cell cycle in mouse development.” Oncogene 24(17): 2877-98.
Croxton, R., Y. Ma, et al. (2002). “Direct repression of the Mcl-1 promoter by E2F1.” Oncogene 21(9): 1359-69.
d’Adda di Fagagna, F. (2008). “Living on a break: cellular senescence as a DNA-damage response.” Nat Rev Cancer 8(7): 512-22.
D’Orazi, G., B. Cecchinelli, et al. (2002). “Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis.” Nat Cell Biol 4(1): 11-9.
de Stanchina, E., M.E. McCurrach, et al. (1998). “E1A signaling to p53 involves the p19(ARF) tumor suppressor.” Genes Dev 12(15): 2434-42.
Deshpande, A., P. Sicinski, et al. (2005). “Cyclins and cdks in development and cancer: a perspective.” Oncogene 24(17): 2909-15.
Di Micco, R., M. Fumagalli, et al. (2006). “Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication.” Nature 444(7119): 638-42.
Egle, A., A.W. Harris, et al. (2004). “Bim is a suppressor of Myc-induced mouse B cell leukemia.” Proc Natl Acad Sci U S A 101(16): 6164-9.
Eilers, M. and R.N. Eisenman (2008). “Myc’s broad reach.” Genes Dev 22(20): 2755-66.
Eischen, C.M., G. Packham, et al. (2001). “Bcl-2 is an apoptotic target suppressed by both c-Myc and E2F-1.” Oncogene 20(48): 6983-93.
Eischen, C.M., J.D. Weber, et al. (1999). “Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis.” Genes Dev 13(20): 2658-69.
Eischen, C.M., D. Woo, et al. (2001). “Apoptosis triggered by Myc-induced suppression of Bcl-X(L) or Bcl-2 is bypassed during lymphomagenesis.” Mol Cell Biol 21(15): 5063-70.
Evan, G.I., A.H. Wyllie, et al. (1992). “Induction of apoptosis in fibroblasts by c-Myc protein.” Cell 69(1): 119-28.
Fernandez, P.C., S.R. Frank, et al. (2003). “Genomic targets of the human c-Myc protein.” Genes Dev 17(9): 1115-29.
Fletcher, T.M. and J.C. Hansen (1995). “Core histone tail domains mediate oligonucleosome folding and nucleosomal DNA organization through distinct molecular mechanisms.” J Biol Chem 270(43): 25359-62.
Fogal, V., J.K. Hsieh, et al. (2005). “Cell cycle-dependent nuclear retention of p53 by E2F1 requires phosphorylation of p53 at Ser315
Frisch, S.M. and J.S. Mymryk (2002). “Adenovirus-5 E1A: paradox and paradigm.” Nat Rev Mol Cell Biol 3(6): 441-52.
Gardner, Lee and Dang (2002). “The c-Myc Oncogenic Transcription Factor”. Adapted from “Myc oncogene”: Encyclopedia of Cancer.
Gartel, A.L. (2009). “p21(WAF1/CIP1) and cancer: a shifting paradigm?” Biofactors 35(2): 161-4.
Grandori, C., N. Gomez-Roman, et al. (2005). “c-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by RNA polymerase I.” Nat Cell Biol 7(3): 311-8.
Guccione, E., F. Martinato, et al. (2006). “Myc-binding-site recognition in the human genome is determined by chromatin context.” Nat Cell Biol 8(7): 764-70.
Harris, A.W., C.A. Pinkert, et al. (1988). “The Eμ-Myc transgenic mouse. A model for high-incidence spontaneous lymphoma and leukemia of early B cells.” J Exp Med 167(2): 353-71.
Haupt, Y., A.I. Robles, et al. (2002). “Deconstruction of p53 functions and regulation.” Oncogene 21(54): 8223-31.
Hayflick, L. and P.S. Moorhead (1961). “The serial cultivation of human diploid cell strains.” Exp Cell Res 25: 585-621.
Hemann, M.T., A. Bric, et al. (2005). “Evasion of the p53 tumour surveillance network by tumour-derived Myc mutants.” Nature 436(7052): 807-11.
Henriksson, M. and B. Luscher (1996). “Proteins of the Myc network: essential regulators of cell growth and differentiation.” Adv Cancer Res 68: 109-82. Herbig, U., W.A. Jobling, et al. (2004). “Telomere shortening triggers senescence
of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a).” Mol Cell 14(4): 501-13.
Herold, S., M. Wanzel, et al. (2002). “Negative regulation of the mammalian UV response by Myc through association with Miz-1.” Mol Cell 10(3): 509-21. Hoffman, B. and D.A. Liebermann (2008). “Apoptotic signaling by c-Myc.”
Oncogene 27(50): 6462-72.
Huang, J., L. Perez-Burgos, et al. (2006). “Repression of p53 activity by Smyd2-mediated methylation.” Nature 444(7119): 629-32.
Janz, S. (2006). “Myc translocations in B cell and plasma cell neoplasms.” DNA Repair (Amst) 5(9-10): 1213-24.
Jimenez, G.S., M. Nister, et al. (2000). “A transactivation-deficient mouse model provides insights into Trp53 regulation and function.” Nat Genet 26(1): 37-43.
Karreth, F.A. and D.A. Tuveson (2009). “Modelling oncogenic RAS/RAF signalling in the mouse.” Curr Opin Genet Dev 19(1): 4-11.
Khan, S.H., J. Moritsugu, et al. (2000). “Differential requirement for p19ARF in the p53-dependent arrest induced by DNA damage, microtubule disruption, and ribonucleotide depletion.” Proc Natl Acad Sci U S A 97(7): 3266-71.
Kim, Y.H., C.Y. Choi, et al. (1998). “Homeodomain-interacting protein kinases, a novel family of co-repressors for homeodomain transcription factors.” J Biol Chem 273(40): 25875-9.
Knights, C.D., J. Catania, et al. (2006). “Distinct p53 acetylation cassettes differentially influence gene-expression patterns and cell fate.” J Cell Biol 173(4): 533-44.
Knoepfler, P.S., P.F. Cheng, et al. (2002). “N-Myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation.” Genes Dev 16(20): 2699-712.
Koumenis, C., R. Alarcon, et al. (2001). “Regulation of p53 by hypoxia: dissociation of transcriptional repression and apoptosis from p53-dependent transactivation.” Mol Cell Biol 21(4): 1297-310.
Kurash, J.K., H. Lei, et al. (2008). “Methylation of p53 by SET7/9 mediates p53 acetylation and activity in vivo.” Mol Cell 29(3): 392-400.
Lawlor, E.R., L. Soucek, et al. (2006). “Reversible kinetic analysis of Myc targets in vivo provides novel insights into Myc-mediated tumorigenesis.” Cancer Res 66(9): 4591-601.
Lee, W.M., M. Schwab, et al. (1985). “Augmented expression of normal c-Myc is sufficient for cotransformation of rat embryo cells with a mutant RAS gene.” Mol Cell Biol 5(12): 3345-56.
Lowe, S.W., E. Cepero, et al. (2004). “Intrinsic tumour suppression.” Nature 432(7015): 307-15.
Lowe, S.W. and C.J. Sherr (2003). “Tumor suppression by Ink4a-Arf: progress and puzzles.” Curr Opin Genet Dev 13(1): 77-83.
Lu, H., Y. Taya, et al. (1998). “Ultraviolet radiation, but not gamma radiation or etoposide-induced DNA damage, results in the phosphorylation of the murine p53 protein at serine-389.” Proc Natl Acad Sci U S A 95(11): 6399-402.
Martinato, F., M. Cesaroni, et al. (2008). “Analysis of Myc-induced histone modifications on target chromatin.” PLoS One 3(11): e3650.
Mateyak, M.K., A.J. Obaya, et al. (1997). “Phenotypes of c-Myc-deficient rat fibroblasts isolated by targeted homologous recombination.” Cell Growth Differ 8(10): 1039-48.
Mathon, N.F. and A.C. Lloyd (2001). “Cell senescence and cancer.” Nat Rev Cancer 1(3): 203-13.
Meyer, N. and L.Z. Penn (2008). “Reflecting on 25 years with Myc.” Nat Rev Cancer 8(12): 976-90.
Michaloglou, C., L.C. Vredeveld, et al. (2005). “BRAFE600-associated senescence-like cell cycle arrest of human naevi.” Nature 436(7051): 720-4. Mihara, M., S. Erster, et al. (2003). “p53 has a direct apoptogenic role at the
mitochondria.” Mol Cell 11(3): 577-90.
Mihara, M. and U.M. Moll (2003). “Detection of mitochondrial localization of p53.” Methods Mol Biol 234: 203-9.
Miyashita, T., S. Krajewski, et al. (1994). “Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo.” Oncogene 9(6): 1799-805.
Morrish, F., N. Neretti, et al. (2008). “The oncogene c-Myc coordinates regulation of metabolic networks to enable rapid cell cycle entry.” Cell Cycle 7(8): 1054-66.
Nahle, Z., J. Polakoff, et al. (2002). “Direct coupling of the cell cycle and cell death machinery by E2F.” Nat Cell Biol 4(11): 859-64.
Nakano, K. and K.H. Vousden (2001). “PUMA, a novel proapoptotic gene, is induced by p53.” Mol Cell 7(3): 683-94.
Nesbit, C.E., J.M. Tersak, et al. (1999). “Myc oncogenes and human neoplastic disease.” Oncogene 18(19): 3004-16.
Nishioka, K., S. Chuikov, et al. (2002). “Set9, a novel histone H3 methyltransferase that facilitates transcription by precluding histone tail modifications required for heterochromatin formation.” Genes Dev 16(4):
Oda, E., R. Ohki, et al. (2000). “Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis.” Science 288(5468): 1053-8.
Oda, K., H. Arakawa, et al. (2000). “p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53.” Cell 102(6): 849-62.
Okamura, S., H. Arakawa, et al. (2001). “p53DINP1, a p53-inducible gene, regulates p53-dependent apoptosis.” Mol Cell 8(1): 85-94.
Ou, Y.H., P.H. Chung, et al. (2005). “p53 C-terminal phosphorylation by CHK1 and CHK2 participates in the regulation of DNA-damage-induced C-terminal acetylation.” Mol Biol Cell 16(4): 1684-95.
Owen-Schaub, L.B., W. Zhang, et al. (1995). “Wild-type human p53 and a temperature-sensitive mutant induce Fas/APO-1 expression.” Mol Cell Biol 15(6): 3032-40.
Patel, J.H., A.P. Loboda, et al. (2004). “Analysis of genomic targets reveals complex functions of Myc.” Nat Rev Cancer 4(7): 562-8.
Perry, M.E. (2004). “Mdm2 in the response to radiation.” Mol Cancer Res 2(1): 9-19.
Popov, N., M. Wanzel, et al. (2007). “The ubiquitin-specific protease USP28 is required for Myc stability.” Nat Cell Biol 9(7): 765-74.
Pusapati, R.V., R.J. Rounbehler, et al. (2006). “ATM promotes apoptosis and suppresses tumorigenesis in response to Myc.” Proc Natl Acad Sci U S A 103(5): 1446-51.
Raj, D., T. Liu, et al. (2008). “Survivin repression by p53, Rb and E2F2 in normal human melanocytes.” Carcinogenesis 29(1): 194-201.
Ricci, M.S., Z. Jin, et al. (2004). “Direct repression of FLIP expression by c-Myc is a major determinant of TRAIL sensitivity.” Mol Cell Biol 24(19): 8541-55. Rinaldo, C., A. Prodosmo, et al. (2007). “MDM2-regulated degradation of HIPK2
prevents p53 Ser46
phosphorylation and DNA damage-induced apoptosis.” Mol Cell 25(5): 739-50.
Rocco, J.W. and D. Sidransky (2001). “p16(MTS-1/CDKN2/INK4a) in cancer progression.” Exp Cell Res 264(1): 42-55.
Sax, J.K., P. Fei, et al. (2002). “BID regulation by p53 contributes to chemosensitivity.” Nat Cell Biol 4(11): 842-9.
Schmitt, C.A., M.E. McCurrach, et al. (1999). “INK4a/ARF mutations accelerate lymphomagenesis and promote chemoresistance by disabling p53.” Genes Dev 13(20): 2670-7.
Seoane, J., H.V. Le, et al. (2002). “Myc suppression of the p21(Cip1) Cdk inhibitor influences the outcome of the p53 response to DNA damage.” Nature 419(6908): 729-34.
Serrano, M., A.W. Lin, et al. (1997). “Oncogenic RAS provokes premature cell senescence associated with accumulation of p53 and p16INK4a.” Cell 88(5): 593-602.
Shah MA, Schwartz GK (2001). “Cell cycle-mediated drug resistance: an emerging concept in cancer therapy”. Clin Cancer Res. Aug; 7: 2168-81.
Staller, P., K. Peukert, et al. (2001). “Repression of p15INK4b expression by Myc through association with Miz-1.” Nat Cell Biol 3(4): 392-9.
Stambolic, V. (2002). “PTEN: a new twist on beta-catenin?” Trends Pharmacol Sci 23(3): 104-6.
Stanelle, J. and B.M. Putzer (2006). “E2F1-induced apoptosis: turning killers into therapeutics.” Trends Mol Med 12(4): 177-85.
Steiger, D., M. Furrer, et al. (2008). “Max-independent functions of Myc in Drosophila melanogaster.” Nat Genet 40(9): 1084-91.
Sykes, S.M., H.S. Mellert, et al. (2006). “Acetylation of the p53 DNA-binding domain regulates apoptosis induction.” Mol Cell 24(6): 841-51.
Tang, Y., J. Luo, et al. (2006). “Tip60-dependent acetylation of p53 modulates the decision between cell-cycle arrest and apoptosis.” Mol Cell 24(6): 827-39. Ueki, K., Y. Ono, et al. (1996). “CDKN2/p16 or RB alterations occur in the
majority of glioblastomas and are inversely correlated.” Cancer Res 56(1): 150-3.
Ventura, A., D.G. Kirsch, et al. (2007). “Restoration of p53 function leads to tumour regression in vivo.” Nature 445(7128): 661-5.
Vogelstein, B., D. Lane, et al. (2000). “Surfing the p53 network.” Nature 408(6810): 307-10.
Vousden, K.H. and C. Prives (2009). “Blinded by the Light: The Growing Complexity of p53.” Cell 137(3): 413-31.
Wang, Y., I.H. Engels, et al. (2004). “Synthetic lethal targeting of Myc by activation of the DR5 death receptor pathway.” Cancer Cell 5(5): 501-12. Webley, K., J.A. Bond, et al. (2000). “Posttranslational modifications of p53 in
replicative senescence overlapping but distinct from those induced by DNA damage.” Mol Cell Biol 20(8): 2803-8.
Wu, G.S., T.F. Burns, et al. (1997). “KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor gene.” Nat Genet 17(2): 141-3.
Yada, M., S. Hatakeyama, et al. (2004). “Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7.” EMBO J 23(10): 2116-25. Yander, G., H. Halsey, et al. (1985). “Amplification and elevated expression of
c-Myc in a chemically induced mouse colon tumor.” Cancer Res 45(9): 4433-8. Yu, J., L. Zhang, et al. (2001). “PUMA induces the rapid apoptosis of colorectal
cancer cells.” Mol Cell 7(3): 673-82.
Zhang, H., P. Gao, et al. (2007). “HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-Myc activity.” Cancer Cell 11(5): 407-20.
Zhao, R., K. Gish, et al. (2000). “The transcriptional program following p53 activation.” Cold Spring Harb Symp Quant Biol 65: 475-82.
Zindy, F., C.M. Eischen, et al. (1998). “Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization.” Genes Dev 12(15): 2424-33.
Zupnick, A. and C. Prives (2006). “Mutational analysis of the p53 core domain L1 loop.” J Biol Chem 281(29): 20464-73.
Ringraziamenti
Ai miei genitori, che con i loro sforzi mi hanno permesso di raggiungere questo traguardo.
A mia Nonna e ai miei zii, in particolar modo zio Maurizio e zia Brunella, per essermi stati sempre vicini e sempre disponibili con me quando ne avevo bisogno.
Ai miei amici: quelli veri, che mi hanno dato tanti ricordi che mi fanno sorridere ogni giorno e mi rendono fiero di avere incontrato persone cosi sul mio cammino.
Un grazie particolare va a Matteo, per essermi stato amico “da sempre” e per esserci stato “sempre”. Grazie a Maurizio, Mario, Nello, Cesare e Federico. Le risate, gli scherzi, le cavolate che ho fatto con loro mi hanno aiutato e continuano ad aiutarmi a ritrovare il sorriso anche nei momenti più difficili. Grazie anche ad Arianna, per esserci sempre stata nei momenti in cui avevo bisogno di parlare con qualcuno. Un grazie speciale va a Nicola, ora in quel di Manhattan, per esserci sempre stato e per avermi sempre dato una mano, specialmente in questo ultimo anno; di sicuro uno dei più duri della mia vita (vorrei augurarmi che i prossimi siano più leggeri… chissà?). Son sicuro che questa sarà una delle poche amicizie nate all’università che si protrarrà nel tempo, e quelle cosi son le poche che veramente valgono. Un altra amicizia pisana che spero resti sempre è la mitica Maddy. Di persone gentili e buone come lei se ne vedono poche in giro… per non parlare dei sui mitici dolcetti.
Al gruppo di Bruno Amati.
A Bruno, per avermi dato la possibilità di fare questa magnifica esperienza e per avermi aiutato, con le sue parole, a trovare il mio primo lavoro. A Stefano, per avermi sempre seguito con la sua pazienza senza limiti, per essere stato il mio maestro per un anno intero e per avermi sempre capito. Sono veramente fiero di aver avuto una persona come lui come supervisor.
A Mirko e Alessandro, e ai sorrisi che durante quest’anno mi hanno fatto fare. A Serena, e al destino che ci ha fatti incontrare in quell’auletta del polo nobili.
Alla Professoressa Dente, e alla sua sempre presente gentilezza e disponibilità nei miei confronti, e alle sue parole, che mi hanno permesso di fare la tesi allo IEO e di trovare un lavoro.
Infine un ringraziamento alle due cose principali in cui credo: alle canzoni di Ligabue, che sanno chi sono meglio di quanto lo sappia io stesso, che partono e mi fanno sentire quello che ho bisogno di sentire semplicemente schiacciando play. E al film “Il corvo” per avermi insegnato a capire e a guardare il grande significato nascosto nelle piccole cose.