{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T07:55:06Z","timestamp":1791186906895,"version":"4.1.0"},"reference-count":164,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2013,11,13]],"date-time":"2013-11-13T00:00:00Z","timestamp":1384300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ionizing radiation triggers diverse responses in human cells encompassing apoptosis, necrosis, stress-induced premature senescence (SIPS), autophagy, and endopolyploidy (e.g., multinucleation). Most of these responses result in loss of colony-forming ability in the clonogenic survival assay. However, not all modes of so-called clonogenic cell \u201cdeath\u201d are necessarily advantageous for therapeutic outcome in cancer radiotherapy. For example, the crosstalk between SIPS and autophagy is considered to influence the capacity of the tumor cells to maintain a prolonged state of growth inhibition that unfortunately can be succeeded by tumor regrowth and disease recurrence. Likewise, endopolyploid giant cells are able to segregate into near diploid descendants that continue mitotic activities. Herein we review the current knowledge on the roles that the p53 and p21WAF1 tumor suppressors play in determining the fate of human fibroblasts (normal and Li-Fraumeni syndrome) and solid tumor-derived cells after exposure to ionizing radiation. In addition, we discuss the important role of WIP1, a p53-regulated oncogene, in the temporal regulation of the DNA damage response and its contribution to p53 dynamics post-irradiation. This article highlights the complexity of the DNA damage response and provides an impetus for rethinking the nature of cancer cell resistance to therapeutic agents.<\/jats:p>","DOI":"10.3390\/ijms141122409","type":"journal-article","created":{"date-parts":[[2013,11,13]],"date-time":"2013-11-13T12:55:52Z","timestamp":1384347352000},"page":"22409-22435","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":104,"title":["Ionizing Radiation-Induced Responses in Human Cells with Differing TP53 Status"],"prefix":"10.3390","volume":"14","author":[{"given":"Razmik","family":"Mirzayans","sequence":"first","affiliation":[{"name":"Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonnie","family":"Andrais","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"April","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Murray","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2013,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1038\/nrm1443","article-title":"Apoptosis and genomic instability","volume":"5","author":"Zhivotovsky","year":"2004","journal-title":"Nat. Rev. Mol. Cell. Biol"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.4161\/auto.25233","article-title":"Cytoprotective and nonprotective autophagy in cancer therapy","volume":"9","author":"Gewitz","year":"2013","journal-title":"Autophagy"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.mrfmmm.2013.07.003","article-title":"The DNA damage response during mitosis","volume":"750","author":"Heijink","year":"2013","journal-title":"Mutat. Res"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5447","DOI":"10.1038\/onc.2010.310","article-title":"MOS, aneuploidy and the ploidy cycle of cancer cells","volume":"29","author":"Erenpreisa","year":"2010","journal-title":"Oncogene"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1101\/gad.12.19.2973","article-title":"The complexity of p53 modulation: Emerging patterns from divergent signals","volume":"12","author":"Giaccia","year":"1998","journal-title":"Genes Dev"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1038\/sj.cdd.4400625","article-title":"Regulation and activation of p53 and its family members","volume":"66","author":"Lohrum","year":"1999","journal-title":"Cell Death Differ"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"170325","DOI":"10.1155\/2012\/170325","article-title":"New insights into p53 signaling and cancer-cell response to DNA damage: Implications for cancer therapy","volume":"2012","author":"Mirzayans","year":"2012","journal-title":"J. Biomed. Biotechnol"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4139","DOI":"10.1242\/jcs.114.23.4139","article-title":"The p53 functional circuit","volume":"114","author":"Jin","year":"2001","journal-title":"J. Cell Sci"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4077","DOI":"10.1242\/jcs.00739","article-title":"Apoptosis\u2014The p53 network","volume":"116","author":"Haupt","year":"2003","journal-title":"J. Cell Sci"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/sj.cdd.4401183","article-title":"Decision making by p53: Life, death and cancer","volume":"10","author":"Oren","year":"2003","journal-title":"Cell Death Differ"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"686","DOI":"10.4161\/cc.6.6.3990","article-title":"Programs for cell death: Apoptosis is only one way to go","volume":"6","author":"Blank","year":"2007","journal-title":"Cell Cycle"},{"key":"ref_12","first-page":"2705","article-title":"Tumor cell senescence in cancer treatment","volume":"63","author":"Roninson","year":"2003","journal-title":"Cancer Res"},{"key":"ref_13","first-page":"2853","article-title":"Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor","volume":"6","author":"Patil","year":"2008","journal-title":"PLoS Biol"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"15931","DOI":"10.3390\/ijms140815931","article-title":"Mechanisms of radiation toxicity in transformed and non-transformed cells","volume":"14","author":"Panganiban","year":"2013","journal-title":"Int. J. Mol. Sci"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"931","DOI":"10.4161\/cc.6.8.4180","article-title":"ATM activation and DNA damage response","volume":"6","author":"Lavin","year":"2007","journal-title":"Cell Cycle"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3894","DOI":"10.1038\/sj.onc.1209426","article-title":"Recruitment of ATR to sites of ionising radiation-induced DNA damage requires ATM and components of the MRN protein complex","volume":"25","author":"Adams","year":"2006","journal-title":"Oncogene"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1084\/jem.20051923","article-title":"ATM regulates ATR chromatin loading in response to DNA double-strand breaks","volume":"203","author":"Cuadrado","year":"2006","journal-title":"J. Exp. Med"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.dnarep.2004.03.024","article-title":"H2AX: The histone guardian of the genome","volume":"3","author":"Lee","year":"2004","journal-title":"DNA Repair"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1038\/nrc2523","article-title":"GammaH2AX and cancer","volume":"8","author":"Bonner","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S1044-579X(02)00099-8","article-title":"The p53-Mdm2 module and the ubiquitin system","volume":"13","author":"Michael","year":"2003","journal-title":"Semin. Cancer Biol"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"22702","DOI":"10.3402\/pba.v3i0.22702","article-title":"p53 as an intervention target for cancer and aging","volume":"3","author":"Hasty","year":"2013","journal-title":"Pathobiol. Aging Age. Relat. Dis"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.4161\/cc.6.9.4211","article-title":"p53: Guardian of the genome and policeman of the oncogenes","volume":"6","author":"Efeyan","year":"2007","journal-title":"Cell Cycle"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6845","DOI":"10.1093\/emboj\/18.23.6845","article-title":"Phosphorylation of human p53 by p38 kinase coordinates N-terminal phosphorylation and apoptosis in response to UV radiation","volume":"18","author":"Bulavin","year":"1999","journal-title":"EMBO J"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12229","DOI":"10.1074\/jbc.274.18.12229","article-title":"p38 kinase mediates UV-induced phosphorylation of p53 protein at serine 389","volume":"274","author":"Huang","year":"1999","journal-title":"J. Biol. Chem"},{"key":"ref_25","first-page":"2464","article-title":"A role for the p38 mitogen-activated protein kinase pathway in the transcriptional activation of p53 on genotoxic stress by chemotherapeutic agents","volume":"60","author":"Rojas","year":"2000","journal-title":"Cancer Res"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2274","DOI":"10.1158\/0008-5472.CAN-06-2884","article-title":"Homeodomain-interacting protein kinase 2 is the ionizing radiation-activated p53 serine 46 kinase and is regulated by ATM","volume":"67","author":"Dauth","year":"2007","journal-title":"Cancer Res"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nrm1546","article-title":"p53: Traffic cop at the crossroads of DNA repair and recombination","volume":"6","author":"Sengupta","year":"2005","journal-title":"Nat. Rev. Mol. Cell Biol"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1038\/sj.cdd.4401910","article-title":"The P53 pathway: What questions remain to be explored?","volume":"13","author":"Levine","year":"2006","journal-title":"Cell Death Differ"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/S0962-8924(00)01834-1","article-title":"The lore of the RINGs: Substrate recognition and catalysis by ubiquitin ligases","volume":"10","author":"Jackson","year":"2000","journal-title":"Trends Cell Biol"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1016\/j.biocel.2007.03.022","article-title":"MDM2 and MDM4: P53 regulators as targets in anticancer therapy","volume":"9","author":"Toledo","year":"2007","journal-title":"Int. J. Biochem. Cell Biol"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1101\/gad.11.15.1974","article-title":"Repression of p53-mediated transcription by MDM2: A dual mechanism","volume":"11","author":"Thut","year":"1997","journal-title":"Genes Dev"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/362857a0","article-title":"Amplification of a gene encoding a p53-associated protein in human sarcomas","volume":"362","author":"Oliner","year":"1993","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s10555-008-9127-x","article-title":"The type 2C phosphatase Wip1: An oncogenic regulator of tumor suppressor and DNA damage response pathways","volume":"27","author":"Lu","year":"2008","journal-title":"Cancer Metastasis Rev"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6048","DOI":"10.1073\/pnas.94.12.6048","article-title":"Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner","volume":"94","author":"Fiscella","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1038\/onc.2009.501","article-title":"Wip1 phosphatase is associated with chromatin and dephosphorylates gammaH2AX to promote checkpoint inhibition","volume":"29","author":"Lindqvist","year":"2010","journal-title":"Oncogene"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"12935","DOI":"10.1074\/jbc.M109.071696","article-title":"Wild-type p53-induced phosphatase 1 dephosphorylates histone variant gamma-H2AX and suppresses DNA double strand break repair","volume":"285","author":"Moon","year":"2010","journal-title":"J. Biol. Chem"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4112","DOI":"10.1158\/0008-5472.CAN-09-4244","article-title":"Wip1 directly dephosphorylates gamma-H2AX and attenuates the DNA damage response","volume":"70","author":"Cha","year":"2010","journal-title":"Cancer Res"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1101\/gad.1291305","article-title":"PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints","volume":"19","author":"Lu","year":"2005","journal-title":"Genes Dev"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6517","DOI":"10.1093\/emboj\/19.23.6517","article-title":"p53-inducible Wip1 phosphatase mediates a negative feedback regulation of p38 MAPK-p53 signaling in response to UV radiation","volume":"19","author":"Takekawa","year":"2000","journal-title":"EMBO J"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1038\/sj.cdd.4401801","article-title":"Regulation of the antioncogenic Chk2 kinase by the oncogenic Wip1 phosphatase","volume":"13","author":"Fujimoto","year":"2006","journal-title":"Cell Death Differ"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.molcel.2006.07.010","article-title":"Wip1 phosphatase modulates ATM-dependent signaling pathways","volume":"3","author":"Shreeram","year":"2006","journal-title":"Mol. Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.ccr.2007.08.033","article-title":"The Wip1 phosphatase acts as a gatekeeper in the p53-Mdm2 autoregulatory loop","volume":"12","author":"Lu","year":"2007","journal-title":"Cancer Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.tcb.2010.01.009","article-title":"The p53 orchestra: Mdm2 and Mdmx set the tone","volume":"20","author":"Wade","year":"2010","journal-title":"Trends Cell Biol"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.cell.2009.04.050","article-title":"Modes of p53 regulation","volume":"137","author":"Kruse","year":"2009","journal-title":"Cell"},{"key":"ref_45","first-page":"88","article-title":"MDM2 and MDMX: Alone and together in regulation of p53","volume":"1","author":"Shadfan","year":"2012","journal-title":"Transl. Cancer Res"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7960","DOI":"10.1158\/0008-5472.CAN-09-0634","article-title":"Phosphorylation and degradation of MdmX is inhibited by Wip1 phosphatase in the DNA damage response","volume":"69","author":"Zhang","year":"2009","journal-title":"Cancer Res"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/ng894","article-title":"Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity","volume":"31","author":"Bulavin","year":"2002","journal-title":"Nat. Genet"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/ng888","article-title":"Oncogenic properties of PPM1D located within a breast cancer amplification epicenter at 17q23","volume":"31","author":"Li","year":"2002","journal-title":"Nat. Genet"},{"key":"ref_49","first-page":"1876","article-title":"PPM1D is a potential target for 17q gain in neuroblastoma","volume":"63","author":"Imoto","year":"2003","journal-title":"Cancer Res"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1126\/science.282.5393.1497","article-title":"Requirement for p53 and p21 to sustain G2 arrest after DNA damage","volume":"282","author":"Bunz","year":"1998","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6954","DOI":"10.1038\/sj.onc.1210516","article-title":"p21Waf1\/Cip1\/Sdi1 mediates retinoblastoma protein degradation","volume":"26","author":"Broude","year":"2007","journal-title":"Oncogene"},{"key":"ref_52","first-page":"639","article-title":"The role of the cyclin-dependent kinase inhibitor p21 in apoptosis","volume":"1","author":"Gartel","year":"2002","journal-title":"Mol. Cancer Ther"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/S1535-6108(03)00308-8","article-title":"p21Waf1\/Cip1 as a therapeutic target in breast and other cancers","volume":"4","author":"Weiss","year":"2003","journal-title":"Cancer Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"11254","DOI":"10.1158\/0008-5472.CAN-06-1569","article-title":"p21 blocks irradiation-induced apoptosis downstream of mitochondria by inhibition of cyclin-dependent kinase-mediated caspase-9 activation","volume":"66","author":"Sohn","year":"2006","journal-title":"Cancer Res"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0304-3835(01)00847-3","article-title":"Oncogenic functions of tumour suppressor p21Waf1\/Cip1\/Sdi1: Association with cell senescence and tumour-promoting activities of stromal fibroblasts","volume":"179","author":"Roninson","year":"2002","journal-title":"Cancer Lett"},{"key":"ref_56","first-page":"M43","article-title":"p21WAF1\/Cip1: More than a break to the cell cycle?","volume":"1471","author":"Dotto","year":"2000","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/2041-9414-2-7","article-title":"Cellular Senescence\u2014Its role in cancer and the response to ionizing radiation","volume":"2","author":"Sabin","year":"2011","journal-title":"Genome Integr"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4291","DOI":"10.1073\/pnas.97.8.4291","article-title":"Effects of p21Waf1\/Cip1\/Sdi1 on cellular gene expression: Implications for carcinogenesis, senescence, and age-related diseases","volume":"97","author":"Chang","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1158\/1078-0432.CCR-07-4298","article-title":"Ataxia telangiectasia mutated and p21CIP1 modulate cell survival of drug-induced senescent tumor cells: Implications for chemotherapy","volume":"14","author":"Crescenzi","year":"2008","journal-title":"Clin. Cancer Res"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"932","DOI":"10.4161\/cc.10.6.15012","article-title":"p21WAF1 is component of a positive feedback loop that maintains the p53 transcriptional program","volume":"10","author":"Pang","year":"2011","journal-title":"Cell Cycle"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1093\/carcin\/23.3.403","article-title":"Human cells deficient in p53 regulated p21waf1\/cip1 expression exhibit normal nucleotide excision repair of UV-induced DNA damage","volume":"23","author":"Wani","year":"2002","journal-title":"Carcinogenesis"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"37849","DOI":"10.1074\/jbc.M204497200","article-title":"Inactivation of p21WAF1 sensitizes cells to apoptosis via an increase of both p14ARF and p53 levels and an alteration of the Bax\/Bcl-2 ratio","volume":"277","author":"Javelaud","year":"2002","journal-title":"J. Biol. Chem"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S0092-8674(00)81401-4","article-title":"ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways","volume":"92","author":"Zhang","year":"1998","journal-title":"Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1093\/emboj\/18.1.22","article-title":"Association of p19(ARF) with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53","volume":"18","author":"Honda","year":"1999","journal-title":"EMBO J"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.4161\/cc.6.12.4313","article-title":"p21 (CDKN1A) is a negative regulator of p53 stability","volume":"6","author":"Broude","year":"2007","journal-title":"Cell Cycle"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/sj.onc.1202271","article-title":"Aberrant p21WAF1-dependent growth arrest as the possible mechanism of abnormal resistance to ultraviolet light cytotoxicity in Li-Fraumeni syndrome fibroblast strains heterozygous for TP53 mutations","volume":"17","author":"Barley","year":"1998","journal-title":"Oncogene"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1667\/RR3280","article-title":"Induction of accelerated senescence following exposure to ionizing radiation in human solid tumor-derived cell lines expressing wild-type","volume":"163","author":"Mirzayans","year":"2005","journal-title":"TP53. Radiat. Res"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/jcp.21284","article-title":"Ultraviolet light exposure triggers nuclear accumulation of p21WAF1 and accelerated senescence in human normal and nucleotide excision repair-deficient fibroblast strains","volume":"215","author":"Mirzayans","year":"2008","journal-title":"J. Cell. Physiol"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2307\/3579639","article-title":"Radiosensitivity in ataxia telangiectasia fibroblasts is not associated with deregulated apoptosis","volume":"150","author":"Enns","year":"1998","journal-title":"Radiat. Res"},{"key":"ref_70","unstructured":"Garvey, R.B. (2009). Cellular Senescence: Implications for Cancer Therapy, Nova Science Publishers, Inc. Monograph."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/ng1293","article-title":"Dynamics of the p53-Mdm2 feedback loop in individual cells","volume":"36","author":"Lahav","year":"2004","journal-title":"Nat. Genet"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.molcel.2008.03.016","article-title":"Recurrent initiation: A mechanism for triggering p53 pulses in response to DNA damage","volume":"9","author":"Batchelor","year":"2008","journal-title":"Mol. Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"12245","DOI":"10.1073\/pnas.0813088106","article-title":"Cell fate decision mediated by p53 pulses","volume":"106","author":"Zhang","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"31571","DOI":"10.1074\/jbc.M110.134650","article-title":"Coordination between cell cycle progression and cell fate decision by the p53 and E2F1 pathways in response to DNA damage","volume":"285","author":"Zhang","year":"2010","journal-title":"J. Biol. Chem"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"8990","DOI":"10.1073\/pnas.1100600108","article-title":"Two-phase dynamics of p53 in the DNA damage response","volume":"108","author":"Zhang","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e38164","DOI":"10.1371\/journal.pone.0038164","article-title":"A two-step mechanism for cell fate decision by coordination of nuclear and mitochondrial p53 activities","volume":"7","author":"Tian","year":"2012","journal-title":"PLoS One"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S0092-8674(00)00073-8","article-title":"p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53","volume":"102","author":"Oda","year":"2000","journal-title":"Cell"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/362847a0","article-title":"p53 is required for radiation-induced apoptosis in mouse thymocytes","volume":"362","author":"Lowe","year":"1993","journal-title":"Nature"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1038\/362849a0","article-title":"Thymocyte apoptosis induced by p53-dependent and independent pathways","volume":"362","author":"Clarke","year":"1993","journal-title":"Nature"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"6728","DOI":"10.1128\/MCB.24.15.6728-6741.2004","article-title":"In vivo mitochondrial p53 translocation triggers a rapid first wave of cell death in response to DNA damage that can precede p53 target gene activation","volume":"24","author":"Erster","year":"2004","journal-title":"Mol. Cell Biol"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"85","DOI":"10.4161\/cc.6.1.3705","article-title":"Exploring mechanisms of the DNA-damage response: P53 pulses and their possible relevance to apoptosis","volume":"6","author":"Zhang","year":"2007","journal-title":"Cell Cycle"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1080\/09553000500077211","article-title":"Dose-response for radiation-induced apoptosis, residual 53BP1 foci and DNA-loop relaxation in human lymphocytes","volume":"81","author":"Torudd","year":"2005","journal-title":"Int. J. Radiat. Biol"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1126\/science.1218351","article-title":"p53 dynamics control cell fate","volume":"336","author":"Purvis","year":"2012","journal-title":"Science"},{"key":"ref_84","first-page":"208","article-title":"Enhancement of gamma radiation-induced cytotoxicity of breast cancer cells by curcumin","volume":"1","author":"Girdhani","year":"2009","journal-title":"Mol. Cell Pharmacol"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1080\/09553000500168549","article-title":"p53-Dependent accelerated senescence induced by ionizing radiation in breast tumour cells","volume":"81","author":"Jones","year":"2005","journal-title":"Int. J. Radiat. Biol"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/(SICI)1098-2744(199809)23:1<1::AID-MC1>3.0.CO;2-Q","article-title":"Relaxed cell-cycle arrests and propagation of unrepaired chromosomal damage in cancer cell lines with wild-type p53","volume":"23","author":"Olivier","year":"1998","journal-title":"Mol. Carcinog"},{"key":"ref_87","first-page":"395","article-title":"Time-dependently expressed markers and the characterization for premature senescence induced by ionizing radiation in MCF7","volume":"24","author":"Kim","year":"2010","journal-title":"Oncol. Rep"},{"key":"ref_88","first-page":"348","article-title":"Reconstitution of caspase 3 sensitizes MCF-7 breast cancer cells to doxorubicin- and etoposide-induced apoptosis","volume":"61","author":"Yang","year":"2001","journal-title":"Cancer Res"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s10549-008-0217-9","article-title":"MCF-7 breast carcinoma cells do not express caspase-3","volume":"117","year":"2009","journal-title":"Breast Cancer Res. Treat"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"7065","DOI":"10.1158\/0008-5472.CAN-04-1082","article-title":"Apoptosis resistance of MCF-7 breast carcinoma cells to ionizing radiation is independent of p53 and cell cycle control but caused by the lack of caspase-3 and a caffeine-inhibitable event","volume":"64","author":"Essmann","year":"2004","journal-title":"Cancer Res"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/S0968-0004(00)89093-3","article-title":"Cellular responses to DNA damage: Cell-cycle checkpoints, apoptosis and the roles of p53 and ATM","volume":"20","author":"Enoch","year":"1995","journal-title":"Trends Biochem. Sci"},{"key":"ref_92","first-page":"4164","article-title":"Loss of a p53-associated G1 checkpoint does not decrease cell survival following DNA damage","volume":"53","author":"Slichenmyer","year":"1993","journal-title":"Cancer Res"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2540","DOI":"10.1101\/gad.8.21.2540","article-title":"DNA damage triggers a prolonged p53-dependent G1 arrest and long-term induction of Cip1 in normal human fibroblasts","volume":"8","author":"Linke","year":"1994","journal-title":"Genes Dev"},{"key":"ref_94","first-page":"1171","article-title":"p53 mediates permanent arrest over multiple cell cycles in response to gamma-irradiation","volume":"57","author":"Linke","year":"1997","journal-title":"Cancer Res"},{"key":"ref_95","first-page":"3761","article-title":"A senescence-like phenotype distinguishes tumor cells that undergo terminal proliferation arrest after exposure to anticancer agents","volume":"59","author":"Chang","year":"1999","journal-title":"Cancer Res"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1667\/0033-7587(2001)155[0248:RISLGA]2.0.CO;2","article-title":"Radiation-induced senescence-like growth arrest requires TP53 function but not telomere shortening","volume":"155","author":"Suzuki","year":"2001","journal-title":"Radiat. Res"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/jcp.22002","article-title":"Single-cell analysis of p16INK4a and p21WAF1 expression suggests distinct mechanisms of senescence in normal human and Li-Fraumeni Syndrome fibroblasts","volume":"223","author":"Mirzayans","year":"2010","journal-title":"J. Cell. Physiol"},{"key":"ref_98","first-page":"2284","article-title":"Senescent human fibroblasts resist programmed cell death, and failure to suppress bcl2 is involved","volume":"55","author":"Wang","year":"1995","journal-title":"Cancer Res"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1038\/sj.cdd.4402091","article-title":"Failure of stress-induced down regulation of Bcl-2 contributes to apoptosis resistance in senescent human diploid fibroblasts","volume":"14","author":"Ryu","year":"2007","journal-title":"Cell Death Differ"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.mad.2007.12.007","article-title":"Progressive apoptosis resistance prior to senescence and control by the anti-apoptotic protein BCL-xL","volume":"129","author":"Rochette","year":"2008","journal-title":"Mech. Ageing Dev"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/ncb714","article-title":"Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis","volume":"4","author":"Cecchinelli","year":"2002","journal-title":"Nat. Cell Biol"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncb715","article-title":"Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2","volume":"4","author":"Hofmann","year":"2002","journal-title":"Nat. Cell Biol"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/sj.cdd.4401764","article-title":"Suppression of UV-induced apoptosis by the human DNA repair protein XPG","volume":"13","author":"Clarkson","year":"2006","journal-title":"Cell Death Differ"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.biocel.2010.12.009","article-title":"Dose-dependent mutual regulation between Wip1 and p53 following UVC irradiation","volume":"43","author":"Xia","year":"2011","journal-title":"Int. J. Biochem. Cell Biol"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/sj.onc.1204132","article-title":"p21waf1\/cip1-null human fibroblasts are deficient in nucleotide excision repair downstream the recruitment of PCNA to DNA repair sites","volume":"20","author":"Stivala","year":"2001","journal-title":"Oncogene"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1002\/mc.20864","article-title":"ATR controls the p21WAF1\/Cip1 protein up-regulation and apoptosis in response to low UV fluences","volume":"51","author":"Hendrayani","year":"2012","journal-title":"Mol. Carcinog"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.mrfmmm.2009.01.010","article-title":"The anti-apoptotic role for p53 following exposure to ultraviolet light does not involve DDB2","volume":"663","author":"Stubbert","year":"2009","journal-title":"Mutat. Res"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"6805","DOI":"10.1038\/sj.onc.1204901","article-title":"P53 plays a protective role against UV- and cisplatin-induced apoptosis in transcription-coupled repair proficient fibroblasts","volume":"20","author":"McKay","year":"2001","journal-title":"Oncogene"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/sj.neo.7900028","article-title":"Role for p53 in the recovery of transcription and protection against apoptosis induced by ultraviolet light","volume":"1","author":"McKay","year":"1999","journal-title":"Neoplasia"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1093\/carcin\/21.3.453","article-title":"Nucleotide excision repair and human syndromes","volume":"21","author":"Hoeijmakers","year":"2000","journal-title":"Carcinogenesis"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1038\/nrm2549","article-title":"Transcription-coupled DNA repair: Two decades of progress and surprises","volume":"9","author":"Hanawalt","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"41","DOI":"10.14712\/fb2011057020041","article-title":"The importance of senescence in ionizing radiation-induced tumour suppression","volume":"57","year":"2011","journal-title":"Folia Biol"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.cell.2005.07.002","article-title":"Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy","volume":"22","author":"Pattingre","year":"2005","journal-title":"Cell"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.4161\/auto.5.8.9896","article-title":"Autophagy, senescence and tumor dormancy in cancer therapy","volume":"5","author":"Gewirtz","year":"2009","journal-title":"Autophagy"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/258427a0","article-title":"Ataxia telangiectasia: A human mutation with abnormal radiation sensitivity","volume":"258","author":"Taylor","year":"1975","journal-title":"Nature"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1093\/hmg\/7.10.1555","article-title":"ATM: From gene to function","volume":"7","author":"Rotman","year":"1998","journal-title":"Hum. Mol. Genet"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/348747a0","article-title":"Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome","volume":"348","author":"Srivastava","year":"1990","journal-title":"Nature"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1038\/bjc.1995.237","article-title":"Abnormal pattern of post-\u03b3-ray DNA replication in radioresistant fibroblast strains from affected members of a cancer-prone family with Li-Fraumeni syndrome","volume":"71","author":"Mirzayans","year":"1995","journal-title":"Br. J. Cancer"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1016\/j.ijrobp.2006.08.064","article-title":"Relationship between DNA double strand break rejoining and cell survival following exposure to ionizing radiation in human fibroblast strains with differing ATM\/p53 function: Implications for the evaluation of clinical radiosensitivity","volume":"66","author":"Mirzayans","year":"2006","journal-title":"Int. J. Radiat. Oncol. Biol. Phys"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1080\/095530098141438","article-title":"The p53-mediated DNA damage response to ionizing radiation in fibroblasts from ataxia-without-telangiectasia patients","volume":"74","author":"Jongmans","year":"1998","journal-title":"Int. J. Radiat. Biol"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1002\/j.1460-2075.1996.tb00550.x","article-title":"p53 is linked directly to homologous recombination processes via RAD51\/RecA protein interaction","volume":"15","author":"Sturzbecher","year":"1996","journal-title":"EMBO J"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"10810","DOI":"10.1158\/0008-5472.CAN-05-0729","article-title":"Evidence for the direct binding of phosphorylated p53 to sites of DNA breaks in vivo","volume":"65","author":"Dellaire","year":"2005","journal-title":"Cancer Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/sj.onc.1200838","article-title":"Cell cycle arrest defect in Li-Fraumeni Syndrome: A mechanism of cancer predisposition?","volume":"14","author":"Williams","year":"1997","journal-title":"Oncogene"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1038\/sj.bjc.6690265","article-title":"Radiation-induced G1 arrest is not defective in fibroblasts from Li-Fraumeni families without TP53 mutations","volume":"79","author":"Boyle","year":"1999","journal-title":"Br. J. Cancer"},{"key":"ref_125","first-page":"1335","article-title":"Transmission of in-vitro radioresistance in a cancer-prone family","volume":"1","author":"Blattner","year":"1981","journal-title":"Lancet"},{"key":"ref_126","first-page":"1400","article-title":"Deregulated apoptosis in ataxia telangiectasia: Association with clinical stigmata and radiosensitivity","volume":"56","author":"Duchaud","year":"1996","journal-title":"Cancer Res"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1093\/carcin\/17.4.691","article-title":"Faulty DNA polymerase \u03b4\/\u025b-mediated excision repair in response to \u03b3 radiation or ultraviolet light in p53-deficient fibroblast strains from affected members of a cancer-prone family with Li-Fraumeni syndrome","volume":"17","author":"Mirzayans","year":"1996","journal-title":"Carcinogenesis"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"8876","DOI":"10.1073\/pnas.92.19.8876","article-title":"Li-Fraumeni syndrome fibroblasts homozygous for p53 mutations are deficient in global DNA repair but exhibit normal transcription-coupled repair and enhanced UV resistance","volume":"92","author":"Ford","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/ng0695-188","article-title":"P53 modulation of TFIIH-associated nucleotide excision repair activity","volume":"10","author":"Wang","year":"1995","journal-title":"Nat. Genet"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"6261","DOI":"10.1158\/0008-5472.CAN-11-0213","article-title":"EGF receptor inhibition radiosensitizes NSCLC cells by inducing senescence in cells sustaining DNA double-strand breaks","volume":"71","author":"Wang","year":"2011","journal-title":"Cancer Res"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"951574","DOI":"10.1155\/2012\/951574","article-title":"Role of p16INK4A in replicative senescence and DNA damage-induced premature senescence in p53-deficient human cells","volume":"2012","author":"Mirzayans","year":"2012","journal-title":"Biochem. Res. Int"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/mc.20005","article-title":"Relationship between the radiosensitizing effect of wortmannin, DNA double-strand break rejoining, and p21WAF1 induction in human normal and tumor-derived cells","volume":"39","author":"Mirzayans","year":"2004","journal-title":"Mol. Carcinog"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"461","DOI":"10.2174\/1568011043352768","article-title":"Tumor cell resistance to DNA-damaging agents: From apoptosis to neosis","volume":"4","author":"Martin","year":"2004","journal-title":"Curr. Med. Chem. Anticancer Agents"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/j.cellbi.2005.10.003","article-title":"Stem cells, senescence, neosis and self-renewal in cancer","volume":"29","author":"Rajaraman","year":"2006","journal-title":"Cell Biol. Int"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.4161\/auto.21610","article-title":"Macroautophagy-aided elimination of chromatin: Sorting of waste, sorting of fate?","volume":"8","author":"Erenpreisa","year":"2012","journal-title":"Autophagy"},{"key":"ref_136","first-page":"7660","article-title":"Neither p21WAF1 nor 14\u20133\u20133 sigma prevents G2 progression to mitotic catastrophe in human colon carcinoma cells after DNA damage, but p21WAF1 induces stable G1 arrest in resulting tetraploid cells","volume":"61","author":"Andreassen","year":"2001","journal-title":"Cancer Res"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1016\/j.cellbi.2007.08.013","article-title":"Cancer: A matter of life cycle?","volume":"31","author":"Erenpreisa","year":"2007","journal-title":"Cell Biol. Int."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1038\/emboj.2010.11","article-title":"Multipolar mitosis of tetraploid cells: Inhibition by p53 and dependency on Mos","volume":"29","author":"Vitale","year":"2010","journal-title":"EMBO J"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"207","DOI":"10.4161\/cbt.3.2.663","article-title":"Neosis: A novel type of cell division in cancer","volume":"3","author":"Sundaram","year":"2004","journal-title":"Cancer Biol. Ther"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/j.cellbi.2005.10.003","article-title":"Neosis\u2014A paradigm of self-renewal in cancer","volume":"29","author":"Rajaraman","year":"2005","journal-title":"Cell Biol. Int"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1016\/j.mehy.2005.05.036","article-title":"Clinically significant cancer evolves from transient mutated and\/or aneuploid neoplasia by cell fusion to form unstable syncytia that give rise to ecologically viable parasite species","volume":"65","author":"Parris","year":"2005","journal-title":"Med. Hypotheses"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1290\/1543-706X(2004)40<150:SCTKDF>2.0.CO;2","article-title":"Spontaneous cell transformation: Karyoplasts derived from multinucleated cells produce new cell growth in senescent human epithelial cell cultures","volume":"40","author":"Walen","year":"2004","journal-title":"In Vitro Cell Dev. Biol. Anim"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/j.cellbi.2005.10.016","article-title":"Budded karyoplasts from multinucleated fibroblast cells contain centrosomes and change their morphology to mitotic cells","volume":"29","author":"Walen","year":"2005","journal-title":"Cell Biol. Int"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"219","DOI":"10.4161\/cbt.3.2.750","article-title":"Neosis and its potential role in cancer development and chemoresistance","volume":"3","author":"Navolanic","year":"2004","journal-title":"Cancer Biol. Ther"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1042\/CBI20100762","article-title":"Polyploid tumour cells elicit paradiploid progeny through depolyploidizing divisions and regulated autophagic degradation","volume":"35","author":"Erenpreisa","year":"2011","journal-title":"Cell Biol. Int"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.1158\/0008-5472.CAN-08-3364","article-title":"Activation of meiosis-specific genes is associated with depolyploidization of human tumor cells following radiation-induced mitotic catastrophe","volume":"69","author":"Ianzini","year":"2009","journal-title":"Cancer Res"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"15","DOI":"10.4137\/CGM.S11333","article-title":"Repopulation of ovarian cancer cells after chemotherapy","volume":"6","author":"Telleria","year":"2013","journal-title":"Cancer Growth Metastasis"},{"key":"ref_148","first-page":"143","article-title":"p53-based anti-cancer therapies: An empty promise?","volume":"12","author":"Desilet","year":"2010","journal-title":"Curr. Issues Mol. Biol"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.mad.2008.04.011","article-title":"Induction of senescence with doxorubicin leads to increased genomic instability of HCT116 cells","volume":"130","author":"Sliwinska","year":"2009","journal-title":"Mech. Ageing Dev"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"2825","DOI":"10.1158\/0008-5472.CAN-04-3137","article-title":"Effects of the mammalian target of rapamycin inhibitor CCI-779 used alone or with chemotherapy on human prostate cancer cells and xenografts","volume":"65","author":"Wu","year":"2005","journal-title":"Cancer Res"},{"key":"ref_151","first-page":"4614","article-title":"Selective estrogen receptor modulators as inhibitors of repopulation of human breast cancer cell lines after chemotherapy","volume":"9","author":"Licun","year":"2003","journal-title":"Clin. Cancer Res"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0065-3233(04)69004-8","article-title":"Coordination of repair, checkpoint, and cell death responses to DNA damage","volume":"69","author":"Wang","year":"2004","journal-title":"Adv. Protein Chem"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1016\/j.surg.2011.09.012","article-title":"Necroptosis is a novel mechanism of radiation-induced cell death in anaplastic thyroid and adrenocortical cancers","volume":"150","author":"Nehs","year":"2011","journal-title":"Surgery"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1097\/MAJ.0b013e31821f978d","article-title":"Molecular machinery of autophagy and its implication in cancer","volume":"343","author":"Li","year":"2012","journal-title":"Am. J. Med. Sci"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"291","DOI":"10.4161\/auto.2835","article-title":"Pathways that regulate autophagy and their role in mediating tumor response to treatment","volume":"2","author":"Paglin","year":"2006","journal-title":"Autophagy"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1097\/CCO.0b013e32835b639e","article-title":"p21WAF1 and tumourigenesis: 20 years after","volume":"25","author":"Warfel","year":"2013","journal-title":"Curr. Opin. Oncol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.molcel.2007.11.015","article-title":"The DNA damage response: ten years after","volume":"28","author":"Harper","year":"2007","journal-title":"Mol. Cell"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1016\/j.febslet.2011.05.013","article-title":"The protein kinase landscape of the DNA damage response","volume":"585","author":"Bensimon","year":"2011","journal-title":"FEBS Lett"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.2174\/156802608786141160","article-title":"Molecular architecture of tumor suppressor p53","volume":"8","author":"Viadiu","year":"2008","journal-title":"Curr. Top. Med. Chem"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1038\/sj.cdd.4401925","article-title":"The complexity of p53 stabilization and activation","volume":"13","author":"Lavin","year":"2006","journal-title":"Cell Death Differ"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"2899","DOI":"10.1038\/sj.onc.1208615","article-title":"The p53 pathway: positive and negative feedback loops","volume":"24","author":"Harris","year":"2005","journal-title":"Oncogene"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.4161\/cc.4.9.1981","article-title":"ATM-mediated phosphorylations inhibit Mdmx\/Mdm2 stabilization by HAUSP in favor of p53 activation","volume":"4","author":"Meulmeester","year":"2005","journal-title":"Cell Cycle"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/cdd.2009.68","article-title":"Mdm2-mediated ubiquitylation: p53 and beyond","volume":"17","author":"Marine","year":"2010","journal-title":"Cell Death Differ"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/nrc2657","article-title":"p21 in cancer: intricate networks and multiple activities","volume":"9","author":"Abbas","year":"2009","journal-title":"Nat. Rev. Cancer"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/14\/11\/22409\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:50:35Z","timestamp":1760219435000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/14\/11\/22409"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,11,13]]},"references-count":164,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2013,11]]}},"alternative-id":["ijms141122409"],"URL":"https:\/\/doi.org\/10.3390\/ijms141122409","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,11,13]]}}}