Genotoxic stress-mediated cell cycle activities for the decision of cellular fate

Cell Cycle

Volumn 10, Issue 19, 2011, Pages 3239-3248

  Erol, Adnan ^a  

^a Erol Project Development House for the Disorders of Energy Metabolism   (Turkey)

Author keywords

c Myc; JNK; mTORC1; mTORC2; p53; Senescence; TGFbeta

Indexed keywords

CELL DNA; CYCLIN DEPENDENT KINASE INHIBITOR; MITOGEN ACTIVATED PROTEIN KINASE KINASE 4; MITOGEN ACTIVATED PROTEIN KINASE KINASE 7; PROTEIN KINASE; PROTEIN KINASE B; PROTEIN P53; TRANSFORMING GROWTH FACTOR BETA;

APOPTOSIS; CARCINOGENESIS; CELL CYCLE; CELL DIVISION; CELL STRESS; DNA DAMAGE; DNA REPAIR; GENETIC TRANSCRIPTION; GENOME; GENOTOXICITY; ONCOGENE C MYC; REVIEW; SENESCENCE; SIGNAL TRANSDUCTION;

EID: 80053454795     PISSN: 15384101     EISSN: 15514005     Source Type: Journal    
DOI: 10.4161/cc.10.19.17460     Document Type: Review

References (112)

1. Salminen A, Kaarniranta K. Genetics vs. entropy: longevity factors suppress the NFkappa-driven entropic aging process. Ageing Res Rev 2010; 9:298-314; PMID:19903538; DOI:10.1016/j.arr.2009.11.001.
2. Diderich K, Alanazi M, Hoeijmakers JH. Premature aging and cancer in nucleotide excision repair-disorders. DNA Repair (Amst) 2011.
3. Bozulic L, Hemmings BA. PIKKing on PKB: regulation of PKB activity by phosphorylation. Curr Opin Cell Biol 2009; 21:256-61; PMID:19303758; DOI:10.1016/j.ceb.2009.02.002.
4. Bozulic L, Surucu B, Hynx D, Hemmings BA. PKBalpha/Akt1 acts downstream of DNA-PK in the DNA double-strand break response and promotes survival. Mol Cell 2008; 30:203-13; PMID:18439899; DOI:10.1016/j.molcel.2008.02.024.
5. Paternot S, Bockstaele L, Bisteau X, Kooken H, Coulonval K, Roger PP. Rb inactivation in cell cycle and cancer: the puzzle of highly regulated activating phosphorylation of CDK4 versus constitutively active CDK-activating kinase. Cell Cycle 2010; 9:689-99; PMID:20107323; DOI:10.4161/cc.9.4.10611.
6. Alvarez-Fernández M, Medema RH. A new role for Cdks in the DNA damage response. Cell Cycle 2010; 9:2915-6; PMID:20714217; DOI:10.4161/cc.9.15. 12700.
7. 1/S phase DNA damage checkpoint. Mol Biol Cell 2008; 19:65-77; PMID:17942597; DOI:10.1091/mbc.E07-06-0525.
8. Deans AJ, Khanna KK, McNees CJ, Mercurio C, Heierhorst J, McArthur GA. Cyclin-dependent kinase 2 functions in normal DNA repair and is therapeutic target in BRCA1-deficient cancers. Cancer Res 2006; 66:8219-26; PMID:16912201; DOI:10.1158/0008-5472.CAN-05-3945.
9. Surucu B, Bozulic L, Hynx D, Parcellier A, Hemmings BA. In vivo analysis of protein kinase B (PKB)/Akt regulation in DNA-PKcs-null mice reveals a role for PKB/Akt in DNA damage response and tumorigenesis. J Biol Chem 2008; 283:30025-33; PMID:18757368; DOI:10.1074/jbc.M803053200.
10. Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell 2007; 129:1261-74; PMID:17604717; DOI:10.1016/j.cell.2007.06.009.
11. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005; 307:1098-101; PMID:15718470; DOI:10.1126/science.1106148.
12. Erol A. Systemic DNA damage response and metabolic syndrome as a premalignant state. Curr Mol Med 2010; 10:321-34; PMID:20334625; DOI:10.2174/156652410791065282.
13. Manning BD. Balancing Akt with S6K: implications for both metabolic diseases and tumorigenesis. J Cell Biol 2004; 167:399-403; PMID:15533996; DOI:10.1083/jcb.200408161.
14. Julien LA, Carriere A, Moreau J, Roux PP. mTORC1-activated S6K1 phosphorylates rictor on threonine 1135 and regulates mTORC2 signaling. Mol Cell Biol 2010; 30:908-21; PMID:19995915; DOI:10.1128/MCB.00601-09.
15. Yung HW, Charnock-Jones DS, Burton GJ. Regulation of Akt phosphorylation at Ser473 and Thr308 by endoplasmic reticulum stress modulates substrate specificity in a severity dependent manner. PLoS ONE 2011; 6:17894; PMID:21445305; DOI:10.1371/journal.pone.0017894.
16. Guertin DA, Stevens DM, Thoreen CC, Burds AA, Kalaany NY, Moffat J, et al. Ablation in mice of the mTORC components raptor, rictor or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1. Dev Cell 2006; 11:859-71; PMID:17141160; DOI:10.1016/j.devcel.2006.10.007.
17. Fang J, Meng Q, Vogt PK, Zhang R, Jiang BH. A downstream kinase of the mammalian target of rapamycin, p70S6K1, regulates human double minute 2 protein phosphorylation and stability. J Cell Physiol 2006; 209:261-5; PMID:16883576; DOI:10.1002/jcp.20749.
18. Huston E, Lynch MJ, Mohamed A, Collins DM, Hill EV, MacLeod R, et al. EPAC and PKA allow cAMP dual control over DNA-PK nuclear translocation. Proc Natl Acad Sci USA 2008; 105:12791-6; PMID:18728186; DOI:10.1073/pnas.0805167105.
19. Boehme KA, Kulikov R, Blattner C. p53 stabilization in response to DNA damage requires Akt/PKB and DNA-PK. Proc Natl Acad Sci USA 2008; 105:7785-90; PMID:18505846; DOI:10.1073/pnas.0703423105.
20. Greer EL, Brunet A. FOXO transcription factors at the interface between longevity and tumor suppression. Oncogene 2005; 24:7410-25; PMID:16288288; DOI:10.1038/sj.onc.1209086.
21. Takai H, Xie Y, De Lange T, Pavletich NP. Tel2 structure and function in the Hsp90-mediated maturation of mTOR and ATR complexes. Genes Dev 2010; 24:2019-30; PMID:20801936; DOI:10.1101/gad.1956410.
22. Guo X, Wang XF. Signaling cross-talk between TGFbeta/BMP and other pathways. Cell Res 2009; 19:71-88; PMID:19002158; DOI:10.1038/cr.2008.302.
23. Rahimi RA, Leof EB. TGFbeta versatility: PI3K as a critical mediator of distinct cell type and context specific responses. Cell Cycle 2009; 8:1813-4; PMID:19471120; DOI:10.4161/cc.8.12.8828.
24. Assinder SJ, Dong Q. Kovacevic, Richardson DR. The TGFbeta, PI3K/Akt and PTEN pathways: established and proposed biochemical integration in prostate cancer. Biochem J 2009; 417:411-21; PMID:19099539; DOI:10.1042/BJ20081610.
25. Zhang YE. Non-Smad pathways in TGFbeta signaling. Cell Res 2009; 19:128-39; PMID:19114990; DOI:10.1038/cr.2008.328.
26. Rahimi RA, Andrianifahanana M, Wilkes MC, Edens M, Kottom TJ, Blenis J, et al. Distinct roles for mammalian target of rapamycin complexes in the fibroblast response to transforming growth factorbeta. Cancer Res 2009; 69:84-93; PMID:19117990; DOI:10.1158/0008-5472.CAN-08-2146.
27. Wang S, Wilkes MC, Leof EB, Hirschberg R. Noncanonical TGFbeta pathways, mTORC1 and Abl, in renal interstitial fibrogenesis. Am J Physiol Renal Physiol 2010; 298:142-9; PMID:19846571; DOI:10.1152/ajprenal.00320.2009.
28. Shi J, Wang DM, Wang CM, Hu Y, Liu AH, Zhang YL, et al. Insulin receptor substrate-1 suppresses transforming growth factor-beta1-mediated epithelial-mesenchymal transition. Cancer Res 2009; 69:7180-7; PMID:19738073; DOI:10.1158/0008-5472.CAN-08-4470.
29. Sabapathy K, Hochedlinger K, Nam SY, Bauer A, Karin M, Wagner EF. Distinct roles for JNK1 and JNK2 in regulating JNK activity and c-Jun-dependent cell proliferation. Mol Cell 2004; 15:713-25; PMID:15350216; DOI:10.1016/j.molcel.2004.08.028.
30. Erol A. Insulin resistance is an evolutionarily conserved physiological mechanism at the cellular level for protection against increased oxidative stress. Bioessays 2007; 29:811-18. (Pubitemid 47204286)
31. 2-terminal protein kinase activity is essential for survival and proliferation of T-cell acute lymphoblastic leukemia cells. Mol Cancer Ther 2009; 8:3214-22; PMID:19996270; DOI:10.1158/1535-7163.MCT-09-0408.
32. Hui L, Zatloukal K, Scheuch H, Stepniak E, Wagner EF. Proliferation of human HCC cells and chemically induced mouse liver cancers requires JNK1-dependent p21 downregulation. J Clin Invest 2008; 118:3943-53; PMID:19033664; DOI:10.1172/JCI37156.
33. Weston CR, Davis RJ. The JNK signal transduction pathway. Curr Opin Cell Biol 2007; 19:142-9; PMID:17303404; DOI:10.1016/j.ceb.2007.02.001.
34. Sabapathy K, Wagner EE. JNK2: a negative regulator of cellular proliferation. Cell Cycle 2004; 3:1520-3; PMID:15611655; DOI:10.4161/cc.3.12. 1315.
35. Haeusgen W, Herdegen T, Waetzig V. Specific regulation of JNK signaling by the novel rat MMK7gamma1 isoform. Cell Signal 2010; 22:1761-72; PMID:20633641; DOI:10.1016/j.cellsig.2010.07.002.
36. Gutierrez GJ, Tsuji T, Chen M, Jiang W, Ronai ZA. Interplay between Cdh1 and JNK activity during the cell cycle. Nat Cell Biol 2010; 12:686-95; PMID:20581839; DOI:10.1038/ncb2071.
37. Wang J, Tang R, Lv M, Wang Q, Zhang X, Guo Y, et al. Defective anchoring of JNK1 in the cytoplasm by MKK7 in Jurkat cells is associated with resistance to Fas-mediated apoptosis. Mol Biol Cell 2011; 22:117-27; PMID:21148294; DOI:10.1091/mbc.E10-06-0492.
38. Tafolla E, Wang S, Wong B, Leong J, kapila YL. JNK1 and JNK2 oppositely regulate p53 in signaling linked to apoptosis triggered by an altered fibronectin matrix. J Biol Chem 2005; 280:19992-9. (Pubitemid 41379528)
39. Essers MA, Weijzen S, De Vries-Smits AM, Saarloos I, De Ruiter ND, Bos JL, et al. FOXO transcription factor activation by oxidative stress mediated by the small GTPase Ral and JNK. EMBO J 2004; 23:4802-12; PMID:15538382; DOI:10.1038/sj.emboj.7600476.
40. Calnan DR, Brunet A. The FoxO code. Oncogene 2008; 27:2276-88; PMID:18391970; DOI:10.1038/onc.2008.21.
41. Dávila D, Torres-Aleman I. Neuronal death by oxidative stress involves activation of FOXO3 through a two-arm pathway that activates stress kinases and attenuates insulin-like growth factor I signaling. Mol Biol Cell 2008; 19:2014-25; PMID:18287535; DOI:10.1091/mbc.E07-08-0811.
42. Rodier F, Campisi J, Bhaumik D. Two faces of p53: aging and tumor suppression. Nucleic Acids Res 2007; 35:7475-84; PMID:17942417; DOI:10.1093/nar/gkm744.
43. De Keizer PL, Laberge RM, Campisi J. p53: Proaging or pro-longevity? Aging 2010; 2:377-9; PMID:20657035.
44. Vousden KH. Alternative fuel-another role for p53 in the regulation of metabolism. Proc Natl Acad Sci USA 2010; 107:7117-8; PMID:20393124; DOI:10.1073/pnas.1002656107.
45. Vigneron A, Vousden KH. p53, ROS and senescence in the control of aging. Aging 2010; 2:471-4; PMID:20729567.
46. Demidenko ZN, Korotchkina LG, Gudkov AV, Blagosklonny MV. Paradoxical suppression of cellular senescence by p53. Proc Natl Acad Sci USA 2010; 107:9660-4; PMID:20457898; DOI:10.1073/pnas.1002298107.
47. Schwartzenberg-Bar-Yoseph F, Armoni M, Karnieli E. The tumor suppressor p53 downregulates glucose transporters GLUT1 and GLUT4 gene expression. Cancer Res 2004; 64:2627-33; PMID:15059920; DOI:10.1158/0008-5472.CAN-03-0846.
48. Bensaad K, Vousden KH. p53: new roles in metabolism. Trends Cell Biol 2007; 17:286-91; PMID:17481900; DOI:10.1016/j.tcb.2007.04.004.
49. Niedernhofer LJ, Robbins PD. Signaling mechanisms involved in the response to genotoxic stress and regulating lifespan. Int J Biochem Cell Biol 2008; 40:176-80; PMID:18023240; DOI:10.1016/j.biocel.2007.10.008.
50. Budanov AV, Karin M. p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. Cell 2008; 134:451-60; PMID:18692468; DOI:10.1016/j.cell.2008.06.028.
51. Korotchkina LG, Leontieva OV, Bukreeva RI, Demidenko ZN, Gudkov AV, Blagosklonny MV. The choice between p53-induced senescence and quiescence is determined in part by the mTOR pathway. Aging 2010; 2:344-52; PMID:20606252.
52. Galluzzi L, Kepp O, Kroemer G. Tp53 and mTOR crosstalk to regulate cellular senescence. Aging 2010; 2:535-7; PMID:20876940.
53. Maki CG. Decision-making by p53 and mTOR. Aging 2010; 2:324-6; PMID:20603526.
54. Leontieva OV, Gudkov AV, Blagosklonny MV. Weak p53 permits senescence during cell cycle arrest. Cell Cycle 2010; 9:4323-7; PMID:21051933; DOI:10.4161/cc.9.21.13584.
55. Serrano M. Shifting senescence into quiescence by turning up p53. Cell Cycle 2010; 9:4256-7; PMID:20980826; DOI:10.4161/cc.9.21.13785.
56. Geng Y, Walls KC, Ghosh AP, Akhtar RS, Klocke BJ, Roth KA. Cytoplasmic p53 and activated Bax regulate p53-dependent, transcription-independent neural precursor cell apoptosis. J Histochem Cytochem 2010; 58:265-75; PMID:19901272; DOI:10.1369/jhc.2009.954024.
57. You H, Yamamoto K, Mak TW. Regulation of transactivation-independent proapoptotic activity of p53 by FOXO3a. Proc Natl Acad Sci USA 2006; 103:9051-6; PMID:16757565; DOI:10.1073/pnas.0600889103.
58. You H, Mak TW. Crosstalk between p53 and FOXO transcription factors. Cell Cycle 2005; 4:37-8; PMID:15611669; DOI:10.4161/cc.4.1.1401.
59. Chipuk JE, Bouchier-hayes L, Kuwana T, Newmeyer DD, Green DR. PUMA couples the nuclear and cytoplasmic proapoptotic function of p53. Science 2005; 309:1732-5; PMID:16151013; DOI:10.1126/science.1114297.
60. Yu J, Zhang L. PUMA, a potent killer with or without p53. Oncogene 2008; 27:71-83; PMID:19641508; DOI:10.1038/onc.2009.45.
61. Chipuk JE, Fisher JC, Dillon CP, Kriwacki RW, Kuwana T, Green DR. Mechanism of apoptosis induction by inhibition of the anti-apoptotic BCL-2 proteins. Proc Natl Acad Sci USA 2008; 105:20327-32; PMID:19074266; DOI:10.1073/pnas.0808036105.
62. Chipuk JE, Green DR. Cytoplasmic p53: Bax and forward. Cell Cycle 2004; 3:429-31; PMID:15020844; DOI:10.4161/cc.3.4.821.
63. Jiang P, Du W, Wang X, Mancusco A, Gao X, Wu M, et al. p53 regulates biosynthesis through direct inactivation of glucose6-phosphate dehydrogenase. Nat Cell Biol 2011; 13:310-6; PMID:21336310; DOI:10.1038/ncb2172.
64. Harris SL, Levine AJ. The p53 pathway: positive and negative feedback loops. Oncogene 2005; 24:2899-908; PMID:15838523; DOI:10.1038/sj.onc.1208615.
65. Horn HF, Vousden KH. Coping with stress: multiple ways to activate p53. Oncogene 2007; 26:1306-16; PMID:17322916; DOI:10.1038/sj.onc.1210263.
66. Vousden KH. Switching from life to death: The Mizing link between Myc and p53. Cancer Cell 2002; 2:351-2; PMID:12450789; DOI:10.1016/S1535-6108(02)00186- 1.
67. Seoane J, Le HV, Massagué J. Myc suppression of the p21Cip1 Cdk inhibitor influences the outcome of the p53 response to DNA damage. Nature 2002; 419:729-34; PMID:12384701; DOI:10.1038/nature01119.
68. Staller P, Peukert K, Kiermaier A, Seoane J, Lukas J, Karsunky H, et al. Repression of p15INK4b expression by Myc through association with Miz-1. Nat Cell Biol 2001; 3:392-9; PMID:11283613; DOI:10.1038/35070076.
69. Patel JH, McMahon SB. BCL2 is a downstream effector of Miz-1 essential for blocking c-Mycinduced apoptosis. J Biol Chem 2007; 282:5-13; PMID:17082179; DOI:10.1074/jbc.M609138200.
70. Jung P, Hermeking H. The c-Myc-AP4-p21 cascade. Cell Cycle 2009; 8:982-9; PMID:19270520; DOI:10.4161/cc.8.7.7949.
71. Herold S, Wanzel M, Beuger V, Frohme C, Beul D, Hillukkala T, et al. Negative regulation of the mammalian UV response by Myc through association with Miz-1. Mol Cell 2002; 10:509-21; PMID:12408820; DOI:10.1016/S1097-2765(02) 00633-0.
72. Adhikary S, Eilers M. Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol 2005; 6:635-45; PMID:16064138; DOI:10.1038/nrm1703.
73. Seoane J, Pouponnot C, Staller P, Schader M, Eilers M, Massagué J. TGFbeta influences Myc, Miz-1 and Smad to control the CDK inhibitor p15INK4b. Nat Cell Biol 2001; 3:400-8. (Pubitemid 32288448)
74. Reynisdóttir I, Polyak K, Iavarone A, Massagué J. Kip/Cip and Ink4 Cdk inhibitors cooperate to induce cell cycle arrest in response to TGFbeta. Genes Dev 1995; 9:1831-45; PMID:7649471; DOI:10.1101/gad.9.15.1831.
75. Erol A. Deciphering the intricate regulatory mechanisms for the cellular choice between cell repair, apoptosis or senescence in response to damaging signals. Cell Signal 2011; 23:1076-81; PMID:21144894; DOI:10.1016/j.cellsig. 2010.11.023.
76. Feng Z, Zhang Hi, Levine AJ, Jin S. The coordinate regulation of the p53 and mTOR pathways in cells. Proc Natl Acad Sci USA 2005; 102:8204-9; PMID:15928081; DOI:10.1073/pnas.0502857102.
77. Leontieva OV, Blagosklonny MV. DNA damaging agents and p53 do not cause senescence in quiescent cells, while consecutive re-activation of mTOR is associated with conversion to senescence. Aging 2010; 2:924-35; PMID:21212465.
78. Schlereth K, Charles JP, Bretz AC, Stiewe T. Life or death: p53-induced apoptosis requires DNA binding cooperativity. Cell Cycle 2010; 9:4068-76; PMID:20948308; DOI:10.4161/cc.9.20.13595.
79. Oleinik NV, Krupenko NI, Krupenko SA. Cooperation between JNK1 and JNK2 in activation of p53 apoptotic pathway. Oncogene 2007; 26:7222-30; PMID:17525747; DOI:10.1038/sj.onc.1210526.
80. van der Horst A, Burgering BM. Stressing the role of FoxO proteins in lifespan and disease. Nat Rev Mol Cell Biol 2007; 8:440-50; PMID:17522590; DOI:10.1038/nrm2190.
81. Tsuruta F, Sunayama J, Mon Y, Hatton S, Shimizu S, Tsujimoto Y, et al. JNK promotes Bax translocation to mitochondria through phosphorylation of 14-3-3 proteins. EMBO J 2004; 23:1889-99; PMID:15071501; DOI:10.1038/sj.emboj.7600194.
82. Das M, Garlick DS, Greiner DL, Davis RJ. The role of JNK in the development of hepatocellular carcinoma. Genes Dev 2011; 25:634-45; PMID:21406557; DOI:10.1101/gad.1989311.
83. Chen P, O'Neal JF, Ebelt ND, Cantrell MA, Mitra S, Nasrazadani A, et al. Jnk2 effects on tumor development, genetic instability and replicative stress in an oncogene-driven mouse mammary tumor model. PLoS ONE 2010; 5:10443; PMID:20454618; DOI:10.1371/journal.pone.0010443.
84. Hettinger K, Vikhanskaya F, Poh MK, Lee MK, De Belle I, Zhang JT, et al. c-Jun promotes cellular survival by suppression of PTEN. Cell Death Differ 2007; 14:218-29; PMID:16676006; DOI:10.1038/sj.cdd.4401946.
85. Zhou Q, Lam PY, Han D, Cadenas E. C-Jun N-terminal kinase regulates mitochondrial bioenergetics by modulating pyruvate dehydrogenase activity in primary cortical neurons. J Neurochem 2008; 104:325-35; PMID:17949412.
86. Schumacher B, Garinis GA, Hoeijmakers JH. Age to survive: DNA damage and aging. Trends Genet 2008; 24:77-85; PMID:18192065; DOI:10.1016/j.tig.2007.11. 004.
87. Wu L, Derynck R. Essential role of TGFbeta signaling in glucose-induced cell hypertrophy. Dev Cell 2009; 17:35-48; PMID:19619490; DOI:10.1016/j.devcel. 2009.05.010.
88. 2+/PKC/ MAPKs and PI3K/Akt/mTOR signal pathways. J Cell Physiol 2010; 224:59-70; PMID:20232305.
89. Goraksha-Hicks P, Rathmell JC. TGFbeta: a new role for an old acTOR. Dev Cell 2009; 17:6-8; PMID:19619487; DOI:10.1016/j.devcel.2009.07.004.
90. Dupont S, Zacchigna L, Adorno M, Soligo S, Volpin D, Piccolo S, et al. Convergence of p53 and TGFbeta signaling networks. Cancer Lett 2004; 213:129-38; PMID:15327827; DOI:10.1016/j.canlet.2004.06.008.
91. Cordenonsi M, Montagner M, Adorno M, Zacchigna L, Martello G, Mamidi A, et al. Integration of TGFbeta and Ras/MAPK signaling through p53 phosphorylation. Science 2007; 315:840-3; PMID:17234915; DOI:10.1126/science. 1135961.
92. Beauvais DM, Rapraeger AC. Syndecan-1 couples the insulin-like growth factor-1 receptor to inside-out integrin activation. J Cell Sci 2010; 123:3796-807; PMID:20971705; DOI:10.1242/jcs.067645.
93. Worthington JJ, Klementowicz JE, Travis MA. TGFbeta: a sleeping giant awoken by integrins. Trends Biochem Sci 2011; 36:47-54; PMID:20870411; DOI:10.1016/j.tibs.2010.08.002.
94. Das F, Ghosh-Choudhury N, Mahimainathan L, Venkatesan B, Feliers D, Riley DJ, et al. Raptorrictor axis in TGFbeta-induced protein synthesis. Cell Signal 2008; 20:409-23; PMID:18068336; DOI:10.1016/j.cellsig.2007.10.027.
95. García-Martínez JM, Alessi DR. mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1). Biochem J 2008; 416:375-85; PMID:18925875; DOI:10.1042/BJ20081668.
96. van der Vos KE, Coffer PJ. FOXO-binding partners: it takes two to tango. Oncogene 2008; 27:2289-99; PMID:18391971; DOI:10.1038/onc.2008.22.
97. Magkou C, Mylona E, Theohari I, Papanikolaou, Markaki S, Nakopoulou L. An immunohistochemical evaluation of phosphorylated Akt at threonine 308 [pAkt(Thr308)] in invasive breast cancer. In Vivo 2007; 21:967-72; PMID:18210742.
98. Alcorn JF, van der Velden J, Brown AL, McElhinney B, Irvin CG, Janssen-Heininger JM. c-Jun N-terminal kinase 1 is required for the development of pulmonary fibrosis. Am J Respir Cell Mol Biol 2009; 40:422-32; PMID:18836136; DOI:10.1165/rcmb.2008-0174OC.
99. Velden JL, Alcorn JF, Guala AS, Badura EC, Janssen-Heininger YM. c-Jun N-terminal kinase 1 promotes transforming growth factor-beta1-induced epithelial-to-mesenchymal transition via control of linker phosphorylation and transcriptional activity of Smad3. Am J Respir Cell Mol Biol 2011; 44:571-81; PMID:20581097; DOI:10.1165/rcmb.2009-0282OC.
100. van Riggelen J, Müller J, Otto T, Beuger V, Yetil A, Choi PS, et al. The interaction between Myc and Miz1 is required to antagonize TGFbeta-dependent autocrine signaling during lymphoma formation and maintenance. Genes Dev 2010; 24:1281-94; PMID:20551174; DOI:10.1101/gad.585710.
101. Cipriano R, Kan CE, Graham J, Danielpour D, Stampfer M, Jackson MW. TGFbeta signaling engages an ATM-CHK2-p53-independent RAS-induced senescence and prevents malignant transformation in human mammary epithelial cells. Proc Natl Acad Sci USA 2011; 108:8668-73; PMID:21555587; DOI:10.1073/pnas.1015022108.
102. Yoshikawa K. Cell cycle regulators in neural stem cells and postmitotic neurons. Neurosci Res 2000; 37:1-14; PMID:10802339; DOI:10.1016/S0168-0102(00) 00101-2.
103. Blagosklonny MV. Cell cycle arrest is not senescence. Aging 2011; 3:94-101; PMID:21297220.
104. Tian B, Yang Q, Mao Z. Phosphorylation of ATM by Cdk6 mediates DNA damage signaling and regulates neuronal death. Nat Cell Biol 2009; 11:211-8; PMID:19151707; DOI:10.1038/ncb1829.
105. Zhang P, Dilley C, Mattson MP. DNA damage responses in neural cells: Focus on the telomere. Neuroscience 2007; 145:1439-48; PMID:17207936; DOI:10.1016/j.neuroscience.2006.11.052.
106. Miller FD, Pozniak CD, Walsh GS. Neural Life and death: an essential role for the p53 family. Cell Death Differ 2000; 7:880-8; PMID:11279533; DOI:10.1038/sj.cdd.4400736.
107. Laine H, Doetzlhofer A, Mantela J, Yikoshi J, Laiho M, Roussel MF, et al. p19(Ink4d) and p21(Cip1) collaborate to maintain the postmitotic state of auditory hair cells, their codeletion leading to DNA damage and p53-mediated apoptosis. J Neurosci 2007; 27:1434-44; PMID:17287518; DOI:10.1523/JNEUROSCI. 4956-06.2007.
108. Erol A. Metabolic syndrome is a real disease and premalignant state induced by oncogenic stresses to block malignant transformation. Med Hypotheses 2010; 74:1038-43; PMID:20097480; DOI:10.1016/j.mehy.2010.01.001.
109. Erol A. Are paradoxical cell cycle activities in neurons and glia related to the metabolic theory of Alzheimer's disease? J Alzheimers Dis 2010; 19:129-35; PMID:20061632.
110. Kirkwood T. Ageing: too fast by mistake. Nature 2006; 444:1015-7; PMID:17183304; DOI:10.1038/4441015a.
111. Blagosklonny MV. Aging: ROS or TOR. Cell Cycle 2008; 7:3344-54; PMID:18971624; DOI:10.4161/cc.7.21.6965.
112. Riggs JE. Carcinogenesis, genetic instability and genomic entropy: insight derived from malignant brain tumor age specific mortality rate dynamics. J Theor Biol 1994; 170:331-8; PMID:7996860; DOI:10.1006/jtbi.1994.1195.