The TP53-activated E3 ligase RNF144B is a tumour suppressor that prevents genomic instability.
Aneuploidy
Cancer
Genomic instability
Tumor suppressor
Journal
Journal of experimental & clinical cancer research : CR
ISSN: 1756-9966
Titre abrégé: J Exp Clin Cancer Res
Pays: England
ID NLM: 8308647
Informations de publication
Date de publication:
29 Apr 2024
29 Apr 2024
Historique:
received:
04
12
2023
accepted:
11
04
2024
medline:
30
4
2024
pubmed:
30
4
2024
entrez:
29
4
2024
Statut:
epublish
Résumé
TP53, the most frequently mutated gene in human cancers, orchestrates a complex transcriptional program crucial for cancer prevention. While certain TP53-dependent genes have been extensively studied, others, like the recently identified RNF144B, remained poorly understood. This E3 ubiquitin ligase has shown potent tumor suppressor activity in murine Eμ Myc-driven lymphoma, emphasizing its significance in the TP53 network. However, little is known about its targets and its role in cancer development, requiring further exploration. In this work, we investigate RNF144B's impact on tumor suppression beyond the hematopoietic compartment in human cancers. Employing TP53 wild-type cells, we generated models lacking RNF144B in both non-transformed and cancerous cells of human and mouse origin. By using proteomics, transcriptomics, and functional analysis, we assessed RNF144B's impact in cellular proliferation and transformation. Through in vitro and in vivo experiments, we explored proliferation, DNA repair, cell cycle control, mitotic progression, and treatment resistance. Findings were contrasted with clinical datasets and bioinformatics analysis. Our research underscores RNF144B's pivotal role as a tumor suppressor, particularly in lung adenocarcinoma. In both human and mouse oncogene-expressing cells, RNF144B deficiency heightened cellular proliferation and transformation. Proteomic and transcriptomic analysis revealed RNF144B's novel function in mediating protein degradation associated with cell cycle progression, DNA damage response and genomic stability. RNF144B deficiency induced chromosomal instability, mitotic defects, and correlated with elevated aneuploidy and worse prognosis in human tumors. Furthermore, RNF144B-deficient lung adenocarcinoma cells exhibited resistance to cell cycle inhibitors that induce chromosomal instability. Supported by clinical data, our study suggests that RNF144B plays a pivotal role in maintaining genomic stability during tumor suppression.
Sections du résumé
BACKGROUND
BACKGROUND
TP53, the most frequently mutated gene in human cancers, orchestrates a complex transcriptional program crucial for cancer prevention. While certain TP53-dependent genes have been extensively studied, others, like the recently identified RNF144B, remained poorly understood. This E3 ubiquitin ligase has shown potent tumor suppressor activity in murine Eμ Myc-driven lymphoma, emphasizing its significance in the TP53 network. However, little is known about its targets and its role in cancer development, requiring further exploration. In this work, we investigate RNF144B's impact on tumor suppression beyond the hematopoietic compartment in human cancers.
METHODS
METHODS
Employing TP53 wild-type cells, we generated models lacking RNF144B in both non-transformed and cancerous cells of human and mouse origin. By using proteomics, transcriptomics, and functional analysis, we assessed RNF144B's impact in cellular proliferation and transformation. Through in vitro and in vivo experiments, we explored proliferation, DNA repair, cell cycle control, mitotic progression, and treatment resistance. Findings were contrasted with clinical datasets and bioinformatics analysis.
RESULTS
RESULTS
Our research underscores RNF144B's pivotal role as a tumor suppressor, particularly in lung adenocarcinoma. In both human and mouse oncogene-expressing cells, RNF144B deficiency heightened cellular proliferation and transformation. Proteomic and transcriptomic analysis revealed RNF144B's novel function in mediating protein degradation associated with cell cycle progression, DNA damage response and genomic stability. RNF144B deficiency induced chromosomal instability, mitotic defects, and correlated with elevated aneuploidy and worse prognosis in human tumors. Furthermore, RNF144B-deficient lung adenocarcinoma cells exhibited resistance to cell cycle inhibitors that induce chromosomal instability.
CONCLUSIONS
CONCLUSIONS
Supported by clinical data, our study suggests that RNF144B plays a pivotal role in maintaining genomic stability during tumor suppression.
Identifiants
pubmed: 38685100
doi: 10.1186/s13046-024-03045-4
pii: 10.1186/s13046-024-03045-4
doi:
Substances chimiques
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Ubiquitin-Protein Ligases
EC 2.3.2.27
RNF144B protein, human
EC 2.3.2.27
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
127Subventions
Organisme : Ministerio de Ciencia e Innovación
ID : PID2021-127710OB-I00
Organisme : 'la Caixa' Foundation
ID : 51110009
Organisme : Agencia Estatal de Investigación
ID : RYC2018-025244-I
Organisme : Agencia Estatal de Investigación
ID : CEX2018-000792-M
Organisme : Fundación Científica Asociación Española Contra el Cáncer
ID : POSTD234858ZADR
Informations de copyright
© 2024. The Author(s).
Références
Cheok CF, Verma CS, Baselga J, Lane DP. Translating p53 into the clinic. Nat Rev Clin Oncol. 2011;8. https://doi.org/10.1038/nrclinonc.2010.174 .
Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, et al. Mutational landscape and significance across 12 major cancer types. Nature. 2013;502(7471):333–9. https://doi.org/10.1038/nature12634 .
doi: 10.1038/nature12634
pubmed: 24132290
pmcid: 3927368
McBride KA, Ballinger ML, Killick E, Kirk J, Tattersall MHN, Eeles RA, et al. Li-Fraumeni syndrome: Cancer risk assessment and clinical management. Nat Rev Clin Oncol. 2014;11. https://doi.org/10.1038/nrclinonc.2014.41 .
Schneider K, Zelley K, Nichols KE, Garber J. Li-Fraumeni Syndrome. 1999. 2019. [updated 2013 Apr 11].
Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery CA, Butel JS, et al. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature. 1992;356:215–21. https://doi.org/10.1038/356215a0 .
doi: 10.1038/356215a0
pubmed: 1552940
Harvey M, McArthur MJ, Montgomery CA, Bradley A, Donehower LA. Genetic background alters the spectrum of tumors that develop in p53‐deficient mice. The FASEB Journal. 1993;7. https://doi.org/10.1096/fasebj.7.10.8344491 .
Jacks T, Remington L, Williams BO, Schmitt EM, Halachmi S, Bronson RT, et al. Tumor spectrum analysis in p53-mutant mice. Curr Biol. 1994;4:1–7. https://doi.org/10.1016/S0960-9822(00)00002-6 .
doi: 10.1016/S0960-9822(00)00002-6
pubmed: 7922305
Aubrey BJ, Kelly GL, Janic A, Herold MJ, Strasser A. How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression? Cell Death Differ. 2018;25:104–13. https://doi.org/10.1038/cdd.2017.169 .
doi: 10.1038/cdd.2017.169
pubmed: 29149101
Fischer M. Census and evaluation of p53 target genes. Oncogene. 2017;36:3943–56. https://doi.org/10.1038/ONC.2016.502 .
doi: 10.1038/ONC.2016.502
pubmed: 28288132
pmcid: 5511239
Kastenhuber ER, Lowe SW. Putting p53 in Context. Cell. 2017;170:1062–78. https://doi.org/10.1016/j.cell.2017.08.028 .
doi: 10.1016/j.cell.2017.08.028
pubmed: 28886379
pmcid: 5743327
Laptenko O, Prives C. Transcriptional regulation by p53: One protein, many possibilities. Cell Death Differ. 2006;13. https://doi.org/10.1038/sj.cdd.4401916 .
Menendez D, Inga A, Resnick MA. The expanding universe of p53 targets. Nat Rev Cancer. 2009;9. https://doi.org/10.1038/nrc2730 .
Bieging KT, Mello SS, Attardi LD. Unravelling mechanisms of p53-mediated tumour suppression. Nat Rev Cancer. 2014;14:359–70. https://doi.org/10.1038/nrc3711 .
doi: 10.1038/nrc3711
pubmed: 24739573
pmcid: 4049238
Brady CA, Jiang D, Mello SS, Johnson TM, Jarvis LA, Kozak MM, et al. Distinct p53 Transcriptional Programs Dictate Acute DNA-Damage Responses and Tumor Suppression. Cell. 2011;145:571–83. https://doi.org/10.1016/j.cell.2011.03.035 .
doi: 10.1016/j.cell.2011.03.035
pubmed: 21565614
pmcid: 3259909
Jeffers JR, Parganas E, Lee Y, Yang C, Wang J, Brennan J, et al. Puma is an essential mediator of p53-dependent and -independent apoptotic pathways. Cancer Cell. 2003;4:321–8.
doi: 10.1016/S1535-6108(03)00244-7
pubmed: 14585359
Li T, Kon N, Jiang L, Tan M, Ludwig T, Zhao Y, et al. Tumor Suppression in the Absence of p53-Mediated Cell-Cycle Arrest, Apoptosis, and Senescence. Cell. 2012;149:1269–83. https://doi.org/10.1016/j.cell.2012.04.026 .
doi: 10.1016/j.cell.2012.04.026
pubmed: 22682249
pmcid: 3688046
Michalak EM, Jansen ES, Happo L, Cragg MS, Tai L, Smyth GK, et al. Puma and to a lesser extent Noxa are suppressors of Myc-induced lymphomagenesis. Cell Death Differ. 2009;16:684–96. https://doi.org/10.1038/cdd.2008.195 .
doi: 10.1038/cdd.2008.195
pubmed: 19148184
Valente LJ, Gray DHD, Michalak EM, Pinon-Hofbauer J, Egle A, Scott CL, et al. p53 Efficiently Suppresses Tumor Development in the Complete Absence of Its Cell-Cycle Inhibitory and Proapoptotic Effectors p21, Puma, and Noxa. Cell Rep. 2013;3:1339–45. https://doi.org/10.1016/j.celrep.2013.04.012 .
doi: 10.1016/j.celrep.2013.04.012
pubmed: 23665218
Villunger A, Michalak EM, Coultas L, Müllauer F, Böck G, Ausserlechner MJ, et al. p53- and Drug-Induced Apoptotic Responses Mediated by BH3-Only Proteins Puma and Noxa. Science. 1979;2003(302):1036–8. https://doi.org/10.1126/science.1090072 .
doi: 10.1126/science.1090072
Best SA, Vandenberg CJ, Abad E, Whitehead L, Guiu L, Ding S, et al. Consequences of Zmat3 loss in c-MYC- and mutant KRAS-driven tumorigenesis. Cell Death Dis. 2020;11. https://doi.org/10.1038/s41419-020-03066-9 .
Bieging-Rolett KT, Attardi LD. Zmat3 splices together p53-dependent tumor suppression. Mol Cell Oncol. 2021;8. https://doi.org/10.1080/23723556.2021.1898523 .
Brennan MS, Brinkmann K, Romero Sola G, Healey G, Gibson L, Gangoda L, et al. Combined absence of TRP53 target genes ZMAT3, PUMA and p21 cause a high incidence of cancer in mice. Cell Death Differ. 2024;31:159–69. https://doi.org/10.1038/s41418-023-01250-w .
doi: 10.1038/s41418-023-01250-w
pubmed: 38110554
Janic A, Valente LJ, Wakefield MJ, Di Stefano L, Milla L, Wilcox S, et al. DNA repair processes are critical mediators of p53-dependent tumor suppression. Nat Med. 2018;24:947–53. https://doi.org/10.1038/s41591-018-0043-5 .
doi: 10.1038/s41591-018-0043-5
pubmed: 29892060
Moon SH, Huang CH, Houlihan SL, Regunath K, Freed-Pastor WA, Morris JP, et al. p53 Represses the Mevalonate Pathway to Mediate Tumor Suppression. Cell. 2019;176:564-580.e19. https://doi.org/10.1016/J.CELL.2018.11.011 .
doi: 10.1016/J.CELL.2018.11.011
pubmed: 30580964
Wang SJ, Li D, Ou Y, Jiang L, Chen Y, Zhao Y, et al. Acetylation Is Crucial for p53-Mediated Ferroptosis and Tumor Suppression. Cell Rep. 2016;17. https://doi.org/10.1016/j.celrep.2016.09.022 .
Janic A, Abad E, Amelio I. Decoding p53 tumor suppression: a crosstalk between genomic stability and epigenetic control? Cell Death Differ. 2024;2024:1–8. https://doi.org/10.1038/s41418-024-01259-9 .
doi: 10.1038/s41418-024-01259-9
Nakamura N. The role of the transmembrane RING finger proteins in cellular and organelle function. Membranes (Basel). 2011;1. https://doi.org/10.3390/membranes1040354 .
Spratt DE, Walden H, Shaw GS. RBR E3 ubiquitin ligases: New structures, new insights, new questions. Biochemical Journal. 2014;458. https://doi.org/10.1042/BJ20140006 .
Wang P, Dai X, Jiang W, Li Y, Wei W. RBR E3 ubiquitin ligases in tumorigenesis. Semin Cancer Biol. 2020;67. https://doi.org/10.1016/j.semcancer.2020.05.002 .
Dove KK, Klevit RE. RING-Between-RING E3 Ligases: Emerging Themes amid the Variations. J Mol Biol. 2017;429. https://doi.org/10.1016/j.jmb.2017.08.008 .
Ho SR, Mahanic CS, Lee YJ, Lin WC. RNF144A, an E3 ubiquitin ligase for DNA-PKcs, promotes apoptosis during DNA damage. Proc Natl Acad Sci U S A. 2014;111. https://doi.org/10.1073/pnas.1323107111 .
Huang J, Xu LG, Liu T, Zhai Z, Shu HB. The p53-inducible E3 ubiquitin ligase p53RFP induces p53-dependent apoptosis. FEBS Lett. 2006;580. https://doi.org/10.1016/j.febslet.2005.09.105 .
Ng CC, Arakawa H, Fukuda S, Kondoh H, Nakamura Y. p53RFP, a p53-inducible RING-finger protein, regulates the stability of p21WAF1. Oncogene. 2003;22. https://doi.org/10.1038/sj.onc.1206586 .
Conforti F, Li Yang A, Cristina Piro M, Mellone M, Terrinoni A, Candi E, et al. PIR2/Rnf144B regulates epithelial homeostasis by mediating degradation of p21 WAF1 and p63. Oncogene. 2013;32. https://doi.org/10.1038/onc.2012.497 .
Taebunpakul P, Sayan BS, Flinterman M, Klanrit P, Gäken J, Odell EW, et al. Apoptin induces apoptosis by changing the equilibrium between the stability of TAp73 and DNp73 isoforms through ubiquitin ligase PIR2. Apoptosis. 2012;17. https://doi.org/10.1007/s10495-012-0720-7 .
Benard G, Neutzner A, Peng G, Wang C, Livak F, Youle RJ, et al. IBRDC2, an IBR-type E3 ubiquitin ligase, is a regulatory factor for Bax and apoptosis activation. EMBO Journal. 2010;29. https://doi.org/10.1038/emboj.2010.39 .
Yang G, Gong Y, Wang Q, Wang L, Zhang X. miR-100 antagonism triggers apoptosis by inhibiting ubiquitination-mediated p53 degradation. Oncogene. 2017;36(8):1023–37. https://doi.org/10.1038/onc.2016.270 .
doi: 10.1038/onc.2016.270
pubmed: 27524417
Ambrogio C, Carmona FJ, Vidal A, Falcone M, Nieto P, Romero OA, et al. Modeling lung cancer evolution and preclinical response by orthotopic mouse allografts. Cancer Res. 2014;74. https://doi.org/10.1158/0008-5472.CAN-14-1606 .
Valencia K, Erice O, Kostyrko K, Hausmann S, Guruceaga E, Tathireddy A, et al. The Mir181ab1 cluster promotes KRAS-driven oncogenesis and progression in lung and pancreas. J Clin Invest. 2020;130:1879–95. https://doi.org/10.1172/JCI129012 .
doi: 10.1172/JCI129012
pubmed: 31874105
pmcid: 7108928
Sato M, Larsen JE, Lee W, Sun H, Shames DS, Dalvi MP, et al. Human lung epithelial cells progressed to malignancy through specific oncogenic manipulations. Molecular Cancer Research. 2013;11. https://doi.org/10.1158/1541-7786.MCR-12-0634-T .
Aubrey BJ, Kelly GL, Kueh AJ, Brennan MS, O’Connor L, Milla L, et al. An inducible lentiviral guide RNA platform enables the identification of tumor-essential genes and tumor-promoting mutations in vivo. Cell Rep. 2015;10:1422–32. https://doi.org/10.1016/J.CELREP.2015.02.002 .
doi: 10.1016/J.CELREP.2015.02.002
pubmed: 25732831
Bankhead P, Loughrey MB, Fernández JA, Dombrowski Y, McArt DG, Dunne PD, et al. QuPath: Open source software for digital pathology image analysis. Sci Rep. 2017;7. https://doi.org/10.1038/s41598-017-17204-5 .
Moretton A, Kourtis S, Gañez Zapater A, Calabrò C, Espinar Calvo ML, Fontaine F, et al. A metabolic map of the DNA damage response identifies PRDX1 in the control of nuclear ROS scavenging and aspartate availability. Mol Syst Biol. 2023;19. https://doi.org/10.15252/msb.202211267 .
Orsburn BC. Proteome discoverer-a community enhanced data processing suite for protein informatics. Proteomes. 2021;9. https://doi.org/10.3390/proteomes9010015 .
Zhang X, Smits AH, Van Tilburg GBA, Ovaa H, Huber W, Vermeulen M. Proteome-wide identification of ubiquitin interactions using UbIA-MS. Nat Protoc. 2018;13. https://doi.org/10.1038/nprot.2017.147 .
Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43. https://doi.org/10.1093/nar/gkv007 .
Wu T, Hu E, Xu S, Chen M, Guo P, Dai Z, et al. clusterProfiler 4.0: A universal enrichment tool for interpreting omics data. Innovation. 2021;2. https://doi.org/10.1016/j.xinn.2021.100141 .
Ewels PA, Peltzer A, Fillinger S, Patel H, Alneberg J, Wilm A, et al. The nf-core framework for community-curated bioinformatics pipelines. Nat Biotechnol. 2020;38. https://doi.org/10.1038/s41587-020-0439-x .
Patel H, et al. nf-core/rnaseq: nf-core/rnaseq v3.0—Silver Shark. 2020.
Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, et al. STAR: Ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29. https://doi.org/10.1093/bioinformatics/bts635 .
Giaccia AJ, Kastan MB. The complexity of p53 modulation: Emerging patterns from divergent signals. Genes Dev. 1998;12. https://doi.org/10.1101/gad.12.19.2973 .
Love MI, Anders S, Kim V, Huber W. RNA-Seq workflow: gene-level exploratory analysis and differential expression. F1000Res. 2015;4. https://doi.org/10.12688/f1000research.7035.1 .
Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15. https://doi.org/10.1186/s13059-014-0550-8 .
Leek JT, Storey JD. Capturing heterogeneity in gene expression studies by surrogate variable analysis. PLoS Genet. 2007;3. https://doi.org/10.1371/journal.pgen.0030161 .
Goldman MJ, Craft B, Hastie M, Repečka K, McDade F, Kamath A, et al. Visualizing and interpreting cancer genomics data via the Xena platform. Nat Biotechnol. 2020;38. https://doi.org/10.1038/s41587-020-0546-8 .
Lonsdale J, Thomas J, Salvatore M, Phillips R, Lo E, Shad S, et al. The Genotype-Tissue Expression (GTEx) project. Nat Genet. 2013;45. https://doi.org/10.1038/ng.2653 .
Fischer M, Schwarz R, Riege K, Decaprio JA, Hoffmann S. TargetGeneReg 2.0: a comprehensive web-atlas for p53, p63, and cell cycle-dependent gene regulation. NAR Cancer. 2022;4. https://doi.org/10.1093/narcan/zcac009 .
Tsherniak A, Vazquez F, Montgomery PG, Weir BA, Kryukov G, Cowley GS, et al. Defining a Cancer Dependency Map. Cell. 2017;170. https://doi.org/10.1016/j.cell.2017.06.010 .
Tonelli C, Morelli MJ, Bianchi S, Rotta L, Capra T, Sabò A, et al. Genome-wide analysis of p53 transcriptional programs in B cells upon exposure to genotoxic stress in vivo. Oncotarget. 2015;6:24611–26. https://doi.org/10.18632/oncotarget.5232 .
doi: 10.18632/oncotarget.5232
pubmed: 26372730
pmcid: 4694782
Younger ST, Kenzelmann-Broz D, Jung H, Attardi LD, Rinn JL. Integrative genomic analysis reveals widespread enhancer regulation by p53 in response to DNA damage. Nucleic Acids Res. 2015;43:4462. https://doi.org/10.1093/nar/gkv284 .
doi: 10.1093/nar/gkv284
Zhang Y, Liu T, Meyer CA, Eeckhoute J, Johnson DS, Bernstein BE, et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 2008;9. https://doi.org/10.1186/gb-2008-9-9-r137 .
Hahne F, Ivanek R. Visualizing genomic data using Gviz and bioconductor. Methods in Molecular Biology. vol. 1418, 2016. https://doi.org/10.1007/978-1-4939-3578-9_16 .
Taylor AM, Shih J, Ha G, Gao GF, Zhang X, Berger AC, et al. Genomic and Functional Approaches to Understanding Cancer Aneuploidy. Cancer Cell. 2018;33. https://doi.org/10.1016/j.ccell.2018.03.007 .
Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102. https://doi.org/10.1073/pnas.0506580102 .
Korotkevich G, Sukhov V, Budin N, Shpak B, Artyomov MN, Sergushichev A. Fast gene set enrichment analysis n.d. https://doi.org/10.1101/060012 .
Carter SL, Eklund AC, Kohane IS, Harris LN, Szallasi Z. A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers. Nat Genet. 2006;38. https://doi.org/10.1038/ng1861 .
Collisson EA, Campbell JD, Brooks AN, Berger AH, Lee W, Chmielecki J, et al. Comprehensive molecular profiling of lung adenocarcinoma: The cancer genome atlas research network. Nature. 2014;511:543–50. https://doi.org/10.1038/nature13385 .
doi: 10.1038/nature13385
Kenzelmann Broz D, Spano Mello S, Bieging KT, Jiang D, Dusek RL, Brady CA, et al. Global genomic profiling reveals an extensive p53-regulated autophagy program contributing to key p53 responses. Genes Dev. 2013;27:1016–31. https://doi.org/10.1101/gad.212282.112 .
doi: 10.1101/gad.212282.112
pubmed: 23651856
pmcid: 3656320
Abbas T, Dutta A. P21 in cancer: Intricate networks and multiple activities. Nat Rev Cancer. 2009;9:400–14. https://doi.org/10.1038/nrc2657 .
doi: 10.1038/nrc2657
pubmed: 19440234
pmcid: 2722839
El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, et al. WAF1, a potential mediator of p53 tumor suppression. Cell. 1993;75. https://doi.org/10.1016/0092-8674(93)90500-P .
Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown JP, et al. Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science. 1979;1998:282. https://doi.org/10.1126/science.282.5393.1497 .
doi: 10.1126/science.282.5393.1497
Mello SS, Valente LJ, Raj N, Seoane JA, Flowers BM, McClendon J, et al. A p53 Super-tumor Suppressor Reveals a Tumor Suppressive p53-Ptpn14-Yap Axis in Pancreatic Cancer. Cancer Cell. 2017;32:460-473.e6. https://doi.org/10.1016/j.ccell.2017.09.007 .
doi: 10.1016/j.ccell.2017.09.007
pubmed: 29017057
pmcid: 5659188
Panatta E, Butera A, Mammarella E, Pitolli C, Mauriello A, Leist M, et al. Metabolic regulation by p53 prevents R-loop-associated genomic instability. Cell Rep. 2022;41. https://doi.org/10.1016/j.celrep.2022.111568 .
Garribba L, Santaguida S. The Dynamic Instability of the Aneuploid Genome. Front Cell Dev Biol. 2022;10. https://doi.org/10.3389/fcell.2022.838928 .
Crozier L, Foy R, Mouery BL, Whitaker RH, Corno A, Spanos C, et al. CDK4/6 inhibitors induce replication stress to cause long‐term cell cycle withdrawal. EMBO J. 2022;41. https://doi.org/10.15252/embj.2021108599 .
McCloy RA, Rogers S, Caldon CE, Lorca T, Castro A, Burgess A. Partial inhibition of Cdk1 in G2 phase overrides the SAC and decouples mitotic events. Cell Cycle. 2014;13. https://doi.org/10.4161/cc.28401 .
El-Deiry WS. The role of p53 in chemosensitivity and radiosensitivity. Oncogene. 2003;22. https://doi.org/10.1038/sj.onc.1206949 .
Zhuang H, Zhang Z, Wang W, Qu H. RNF144B-mediated p21 degradation regulated by HDAC3 contribute to enhancing ovarian cancer growth and metastasis. Tissue Cell. 2024;86: 102277. https://doi.org/10.1016/j.tice.2023.102277 .
doi: 10.1016/j.tice.2023.102277
pubmed: 37992458
Naso FD, Sterbini V, Crecca E, Asteriti IA, Russo AD, Giubettini M, et al. Excess TPX2 Interferes with Microtubule Disassembly and Nuclei Reformation at Mitotic Exit. Cells. 2020;9. https://doi.org/10.3390/cells9020374 .
Broderick R, Nieminuszczy J, Blackford AN, Winczura A, Niedzwiedz W. TOPBP1 recruits TOP2A to ultra-fine anaphase bridges to aid in their resolution. Nat Commun. 2015;6. https://doi.org/10.1038/ncomms7572 .
Panigrahi AK, Zhang N, Mao Q, Pati D. Calpain-1 Cleaves Rad21 To Promote Sister Chromatid Separation. Mol Cell Biol. 2011;31. https://doi.org/10.1128/mcb.06075-11 .
Sane S, Rezvani K. Essential roles of E3 ubiquitin ligases in p53 regulation. Int J Mol Sci. 2017;18. https://doi.org/10.3390/ijms18020442 .
Jain AK, Barton MC. Making sense of ubiquitin ligases that regulate p53. Cancer Biol Ther. 2010;10. https://doi.org/10.4161/cbt.10.7.13445 .
Duijf PHG, Benezra R. The cancer biology of whole-chromosome instability. Oncogene. 2013;32. https://doi.org/10.1038/onc.2012.616 .
Lee AJX, Endesfelder D, Rowan AJ, Walther A, Birkbak NJ, Futreal PA, et al. Chromosomal instability confers intrinsic multidrug resistance. Cancer Res. 2011;71. https://doi.org/10.1158/0008-5472.CAN-10-3604 .
Aylon Y, Oren M. P53: Guardian of ploidy. Mol Oncol. 2011;5. https://doi.org/10.1016/j.molonc.2011.07.007 .
Drost J, Van Jaarsveld RH, Ponsioen B, Zimberlin C, Van Boxtel R, Buijs A, et al. Sequential cancer mutations in cultured human intestinal stem cells. Nature. 2015;521. https://doi.org/10.1038/nature14415 .
Kuznetsova AY, Seget K, Moeller GK, de Pagter MS, de Roos JADM, Dürrbaum M, et al. Chromosomal instability, tolerance of mitotic errors and multidrug resistance are promoted by tetraploidization in human cells. Cell Cycle. 2015;14. https://doi.org/10.1080/15384101.2015.1068482 .
Valente LJ, Tarangelo A, Li AM, Naciri M, Raj N, Boutelle AM, et al. p53 deficiency triggers dysregulation of diverse cellular processes in physiological oxygen. J Cell Biol. 2020;219. https://doi.org/10.1083/jcb.201908212 .
Vitale I, Senovilla L, Jema M, Michaud M, Galluzzi L, Kepp O, et al. Multipolar mitosis of tetraploid cells: Inhibition by p53 and dependency on Mos. EMBO Journal. 2010;29. https://doi.org/10.1038/emboj.2010.11 .
Crockford A, Zalmas LP, Grönroos E, Dewhurst SM, McGranahan N, Cuomo ME, et al. Cyclin D mediates tolerance of genome-doubling in cancers with functional p53. Annals of Oncology. 2017;28. https://doi.org/10.1093/annonc/mdw612 .
Narkar A, Johnson BA, Bharne P, Zhu J, Padmanaban V, Biswas D, et al. On the role of p53 in the cellular response to aneuploidy. Cell Rep. 2021;34. https://doi.org/10.1016/j.celrep.2021.108892 .
Potapova TA, Seidel CW, Box AC, Rancati G, Li R. Transcriptome analysis of tetraploid cells identifes cyclin D2 as a facilitator of adaptation to genome doubling in the presence of p53. Mol Biol Cell. 2016;27. https://doi.org/10.1091/mbc.E16-05-0268 .
Sanz-Gómez N, de Pedro I, Ortigosa B, Santamaría D, Malumbres M, de Cárcer G, et al. Squamous differentiation requires G2/mitosis slippage to avoid apoptosis. Cell Death Differ. 2020;27. https://doi.org/10.1038/s41418-020-0515-2 .
Sasai K, Treekitkarnmongkol W, Kai K, Katayama H, Sen S. Functional significance of Aurora kinases-p53 protein family interactions in cancer. Front Oncol. 2016;6. https://doi.org/10.3389/fonc.2016.00247 .
Zeng J, Hills SA, Ozono E, Diffley JFX. Cyclin E-induced replicative stress drives p53-dependent whole-genome duplication. Cell. 2023;186. https://doi.org/10.1016/j.cell.2022.12.036 .
Samora CP, Mogessie B, Conway L, Ross JL, Straube A, McAinsh AD. MAP4 and CLASP1 operate as a safety mechanism to maintain a stable spindle position in mitosis. Nat Cell Biol. 2011;13. https://doi.org/10.1038/ncb2297 .
Huhn SC, Liu J, Ye C, Lu H, Jiang X, Feng X, et al. Regulation of spindle integrity and mitotic fidelity by BCCIP. Oncogene. 2017;36. https://doi.org/10.1038/onc.2017.92 .
Liu S, Yuan X, Gui P, Liu R, Durojaye O, Hill DL, et al. Mad2 promotes Cyclin B2 recruitment to the kinetochore for guiding accurate mitotic checkpoint. EMBO Rep. 2022;23. https://doi.org/10.15252/embr.202154171 .
Zhu C, Jiang W. Cell cycle-dependent translocation of PRC1 on the spindle by Kif4 is essential for midzone formation and cytokinesis. Proc Natl Acad Sci U S A. 2005;102. https://doi.org/10.1073/pnas.0408438102 .