Regulation of p53 and Rb Links the Alternative NF-κB Pathway to EZH2 Expression and Cell Senescence

PLoS Genetics

Volumn 10, Issue 9, 2014, Pages

  Iannetti, Alessio ^a   Ledoux, Adeline C ^a,e   Tudhope, Susan J ^a   Sellier, Hélène ^a   Zhao, Bo ^b   Mowla, Sophia ^c   Moore, Adam ^a   Hummerich, Holger ^c   Gewurz, Benjamin E ^b   Cockell, Simon J ^d   Jat, Parmjit S ^c   Willmore, Elaine ^a   Perkins, Neil D ^a  

^a NEWCASTLE UNIVERSITY   (United Kingdom)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

^c UNIVERSITY COLLEGE LONDON   (United Kingdom)

^d NEWCASTLE UNIVERSITY   (United Kingdom)

^e INSTITUT DE PHARMACOLOGIE ET DE BIOLOGIE STRUCTURALE   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ATM PROTEIN; CD40 LIGAND; CYCLIN DEPENDENT KINASE 4; CYCLIN DEPENDENT KINASE 6; CYCLIN DEPENDENT KINASE INHIBITOR 1; CYCLIN DEPENDENT KINASE INHIBITOR 2A; EPIGALLOCATECHIN GALLATE; I KAPPA B KINASE GAMMA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MANGANESE SUPEROXIDE DISMUTASE; MESSENGER RNA; POLYCOMB REPRESSIVE COMPLEX 2; PROTEIN CDC42; PROTEIN MDM2; PROTEIN P52; PROTEIN P53; RAC PROTEIN; REACTIVE OXYGEN METABOLITE; RETINOBLASTOMA PROTEIN; SMALL INTERFERING RNA; TRANSCRIPTION FACTOR EZH2; TRANSCRIPTION FACTOR RELA; TRANSCRIPTION FACTOR RELB; EZH2 PROTEIN, HUMAN; PROTEIN BINDING; TRANSCRIPTOME;

ARTICLE; B CELL LEUKEMIA; CELL AGING; CELL CYCLE; CELL IMMORTALIZATION; CHROMATIN IMMUNOPRECIPITATION; CHRONIC LYMPHATIC LEUKEMIA; CONTROLLED STUDY; DNA DAMAGE; DOWN REGULATION; FIBROBLAST; GENE REGULATORY NETWORK; HUMAN; HUMAN CELL; MICROARRAY ANALYSIS; MOLECULAR INTERACTION; NUCLEOTIDE SEQUENCE; OXIDATIVE STRESS; PHENOTYPE; POLYMERASE CHAIN REACTION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN STABILITY; QUANTITATIVE ANALYSIS; SIGNAL TRANSDUCTION; WESTERN BLOTTING; AGONISTS; BIOLOGICAL MODEL; CLUSTER ANALYSIS; ENZYME ACTIVATION; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETIC TRANSCRIPTION; GENETICS; METABOLISM; RNA INTERFERENCE;

CD40 LIGAND; CELL AGING; CLUSTER ANALYSIS; ENZYME ACTIVATION; FIBROBLASTS; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; HUMANS; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MODELS, BIOLOGICAL; NF-KAPPA B; NF-KAPPA B P52 SUBUNIT; POLYCOMB REPRESSIVE COMPLEX 2; PROTEIN BINDING; PROTEIN STABILITY; REACTIVE OXYGEN SPECIES; RETINOBLASTOMA PROTEIN; RNA INTERFERENCE; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTOR RELB; TRANSCRIPTION, GENETIC; TRANSCRIPTOME; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84907573587     PISSN: 15537390     EISSN: 15537404     Source Type: Journal    
DOI: 10.1371/journal.pgen.1004642     Document Type: Article

References (64)

1. Hayden MS, Ghosh S, (2008) Shared principles in NF-κB signaling. Cell 132: 344–362.
2. Perkins ND, (2007) Integrating cell-signalling pathways with NF-κB and IKK function. Nat Rev Mol Cell Biol 8: 49–62.
3. Ben-Neriah Y, Karin M, (2011) Inflammation meets cancer, with NF-κB as the matchmaker. Nat Immunol 12: 715–723.
4. Perkins ND, (2012) The diverse and complex roles of NF-κB subunits in cancer. Nat Rev Cancer 12: 121–132.
5. Vaughan S, Jat PS, (2011) Deciphering the role of nuclear factor-κB in cellular senescence. Aging 3: 913–919.
6. Chien Y, Scuoppo C, Wang X, Fang X, Balgley B, et al. (2011) Control of the senescence-associated secretory phenotype by NF-κB promotes senescence and enhances chemosensitivity. Genes Dev 25: 2125–2136.
7. Jing H, Kase J, Dorr JR, Milanovic M, Lenze D, et al. (2011) Opposing roles of NF-κB in anti-cancer treatment outcome unveiled by cross-species investigations. Genes Dev
8. Sfikas A, Batsi C, Tselikou E, Vartholomatos G, Monokrousos N, et al. (2012) The canonical NF-κB pathway differentially protects normal and human tumor cells from ROS-induced DNA damage. Cellular Signalling 24: 2007–2023.
9. Dey A, Tergaonkar V, Lane DP, (2008) Double-edged swords as cancer therapeutics: simultaneously targeting p53 and NF-κB pathways. Nat Rev Drug Discov 7: 1031–1040.
10. Ak P, Levine AJ, (2010) p53 and NF-κB: different strategies for responding to stress lead to a functional antagonism. FASEB J 24: 3643–3652.
11. Schneider G, Kramer OH, (2011) NFκB/p53 crosstalk-a promising new therapeutic target. Biochim Biophys Acta 1815: 90–103.
12. Vigneron A, Vousden KH, (2010) p53, ROS and senescence in the control of aging. Aging (Albany NY) 2: 471–474.
13. Rocha S, Martin AM, Meek DW, Perkins ND, (2003) p53 represses cyclin D1 transcription through down regulation of Bcl-3 and inducing increased association of the p52 NF-κB subunit with histone deacetylase 1. Mol Cell Biol 23: 4713–4727.
14. Schumm K, Rocha S, Caamano J, Perkins ND, (2006) Regulation of p53 tumour suppressor target gene expression by the p52 NF-κB subunit. EMBO J 25: 4820–4832.
15. Shetty S, Graham BA, Brown JG, Hu X, Vegh-Yarema N, et al. (2005) Transcription factor NF-κB differentially regulates death receptor 5 expression involving histone deacetylase 1. Mol Cell Biol 25: 5404–5416.
16. Frank AK, Leu JI, Zhou Y, Devarajan K, Nedelko T, et al. (2011) The codon 72 polymorphism of p53 regulates interaction with NF-κB and transactivation of genes involved in immunity and inflammation. Mol Cell Biol 31: 1201–1213.
17. De Santa F, Narang V, Yap ZH, Tusi BK, Burgold T, et al. (2009) Jmjd3 contributes to the control of gene expression in LPS-activated macrophages. EMBO J 28: 3341–3352.
18. Tang X, Milyavsky M, Shats I, Erez N, Goldfinger N, et al. (2004) Activated p53 suppresses the histone methyltransferase EZH2 gene. Oncogene 23: 5759–5769.
19. Bracken AP, Pasini D, Capra M, Prosperini E, Colli E, et al. (2003) EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer. EMBO J 22: 5323–5335.
20. Chase A, Cross NC, (2011) Aberrations of EZH2 in cancer. Clin Cancer Res 17: 2613–2618.
21. Bracken AP, Kleine-Kohlbrecher D, Dietrich N, Pasini D, Gargiulo G, et al. (2007) The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. Genes Dev 21: 525–530.
22. Fan T, Jiang S, Chung N, Alikhan A, Ni C, et al. (2011) EZH2-dependent suppression of a cellular senescence phenotype in melanoma cells by inhibition of p21/CDKN1A expression. Mol Cancer Res 9: 418–429.
23. Tzatsos A, Paskaleva P, Lymperi S, Contino G, Stoykova S, et al. (2011) Lysine-specific demethylase 2B (KDM2B)-let-7-enhancer of zester homolog 2 (EZH2) pathway regulates cell cycle progression and senescence in primary cells. J Biol Chem 286: 33061–33069.
24. Margueron R, Reinberg D, (2011) The Polycomb complex PRC2 and its mark in life. Nature 469: 343–349.
25. Lanigan F, Geraghty JG, Bracken AP, (2011) Transcriptional regulation of cellular senescence. Oncogene 30: 2901–2911.
26. Lee ST, Li Z, Wu Z, Aau M, Guan P, et al. (2011) Context-Specific Regulation of NF-κB Target Gene Expression by EZH2 in Breast Cancers. Mol Cell 43: 798–810.
27. Guo Z, Kozlov S, Lavin MF, Person MD, Paull TT, (2010) ATM activation by oxidative stress. Science 330: 517–521.
28. Shih VF, Davis-Turak J, Macal M, Huang JQ, Ponomarenko J, et al. (2012) Control of RelB during dendritic cell activation integrates canonical and noncanonical NF-κB pathways. Nat Immunol 13: 1162–1170.
29. Pepper C, Mahdi JG, Buggins AG, Hewamana S, Walsby E, et al. (2011) Two novel aspirin analogues show selective cytotoxicity in primary chronic lymphocytic leukaemia cells that is associated with dual inhibition of Rel A and COX-2. Cell Prolif 44: 380–390.
30. Hostager BS, Bishop GA, (2013) CD40-Mediated Activation of the NF-κB2 Pathway. Front Immunol 4: 376.
31. Freund A, Laberge RM, Demaria M, Campisi J, (2012) Lamin B1 loss is a senescence-associated biomarker. Mol Biol Cell 23: 2066–2075.
32. Rovillain E, Mansfield L, Caetano C, Alvarez-Fernandez M, Caballero OL, et al. (2011) Activation of Nuclear Factor-κB signalling promotes cellular senescence. Oncogene 30: 2356–2366.
33. Kavanaugh GM, Wise-Draper TM, Morreale RJ, Morrison MA, Gole B, et al. (2011) The human DEK oncogene regulates DNA damage response signaling and repair. Nucleic Acids Res 39: 7465–7476.
34. Liu K, Feng T, Liu J, Zhong M, Zhang S, (2012) Silencing of the DEK gene induces apoptosis and senescence in CaSki cervical carcinoma cells via the up-regulation of NF-κB p65. Biosci Rep 32: 323–332.
35. Raptis L, Arulanandam R, Geletu M, Turkson J, (2011) The R(h)oads to Stat3: Stat3 activation by the Rho GTPases. Exp Cell Res 317: 1787–1795.
36. Cheng G, Diebold BA, Hughes Y, Lambeth JD, (2006) Nox1-dependent reactive oxygen generation is regulated by Rac1. J Biol Chem 281: 17718–17726.
37. Qian Y, Liu KJ, Chen Y, Flynn DC, Castranova V, et al. (2005) Cdc42 regulates arsenic-induced NADPH oxidase activation and cell migration through actin filament reorganization. J Biol Chem 280: 3875–3884.
38. Polager S, Ginsberg D, (2008) E2F - at the crossroads of life and death. Trends Cell Biol 18: 528–535.
39. Ledoux AC, Sellier H, Gillies K, Iannetti A, James J, et al. (2013) NFκB regulates expression of Polo-like kinase 4. Cell Cycle 12: 3052–3062.
40. Zhao B, Barrera LA, Ersing I, Willox B, Schmidt SCS, et al. (2014) The NF-κB Genomic Landscape in Lymphoblastoid B-cells. Cell Reports In Press.
41. Tergaonkar V, Pando M, Vafa O, Wahl G, Verma I, (2002) p53 stabilization is decreased upon NFκB activation: a role for NFκB in acquisition of resistance to chemotherapy. Cancer Cell 1: 493–503.
42. Arlt A, Sebens S, Krebs S, Geismann C, Grossmann M, et al. (2013) Inhibition of the Nrf2 transcription factor by the alkaloid trigonelline renders pancreatic cancer cells more susceptible to apoptosis through decreased proteasomal gene expression and proteasome activity. Oncogene 32: 4825–4835.
43. Song MS, Carracedo A, Salmena L, Song SJ, Egia A, et al. (2011) Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner. Cell 144: 187–199.
44. Vu D, Huang DB, Vemu A, Ghosh G, (2013) A structural basis for selective dimerization by NF-κB RelB. J Mol Biol 425: 1934–1945.
45. Annunziata CM, Davis RE, Demchenko Y, Bellamy W, Gabrea A, et al. (2007) Frequent engagement of the classical and alternative NF-κB pathways by diverse genetic abnormalities in multiple myeloma. Cancer Cell 12: 115–130.
46. Demchenko YN, Glebov OK, Zingone A, Keats JJ, Bergsagel PL, et al. (2010) Classical and/or alternative NF-κB pathway activation in multiple myeloma. Blood 115: 3541–3552.
47. Gilmore TD, (2007) Multiple myeloma: lusting for NF-κB. Cancer Cell 12: 95–97.
48. Migliazza A, Lombardi L, Rocchi M, Trecca D, Chang CC, et al. (1994) Heterogeneous chromosomal aberrations generate 3′ truncations of the NFKB2/lyt-10 gene in lymphoid malignancies. Blood 84: 3850–3860.
49. Thakur S, Lin H, Tseng W, Kumar S, Bravo R, et al. (1994) Rearrangement and altered expression of the NFKB-2 gene in human cutaneous T-lymphoma cells. Oncogene 9: 2335–2344.
50. Homig-Holzel C, Hojer C, Rastelli J, Casola S, Strobl LJ, et al. (2008) Constitutive CD40 signaling in B cells selectively activates the noncanonical NF-κB pathway and promotes lymphomagenesis. J Exp Med 205: 1317–1329.
51. Pospisilova S, Gonzalez D, Malcikova J, Trbusek M, Rossi D, et al. (2012) ERIC recommendations on TP53 mutation analysis in chronic lymphocytic leukemia. Leukemia 26: 1458–1461.
52. Beguelin W, Popovic R, Teater M, Jiang Y, Bunting KL, et al. (2013) EZH2 Is Required for Germinal Center Formation and Somatic EZH2 Mutations Promote Lymphoid Transformation. Cancer Cell 23: 677–692.
53. Braun T, Carvalho G, Fabre C, Grosjean J, Fenaux P, et al. (2006) Targeting NF-κB in hematologic malignancies. Cell Death Differ 13: 748–758.
54. Fuchs O, (2010) Transcription factor NF-κB inhibitors as single therapeutic agents or in combination with classical chemotherapeutic agents for the treatment of hematologic malignancies. Curr Mol Pharmacol 3: 98–122.
55. Keutgens A, Robert I, Viatour P, Chariot A, (2006) Deregulated NF-κB activity in haematological malignancies. Biochem Pharmacol 72: 1069–1080.
56. Du P, Kibbe WA, Lin SM, (2008) lumi: a pipeline for processing Illumina microarray. Bioinformatics 24: 1547–1548.
57. Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, et al. (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5: R80.
58. Smyth GK (2005) Limma: linear models for microarray data. In: Gentleman RC, Carey VJ, Dudoit S, Irizarry R, Huber W, editors. ‘Bioinformatics and Computational Biology Solutions using R and Bioconductor. New York: Springer. pp. 397–420.
59. Dimri GP, Lee X, Basile G, Acosta M, Scott G, et al. (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A 92: 9363–9367.
60. Lyons AB, Parish CR, (1994) Determination of lymphocyte division by flow cytometry. J Immunol Methods 171: 131–137.
61. Pfaffl MW, (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29: e45.
62. Langmead B, Trapnell C, Pop M, Salzberg SL, (2009) Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 10: R25.
63. Robinson JT, Thorvaldsdottir H, Winckler W, Guttman M, Lander ES, et al. (2011) Integrative genomics viewer. Nat Biotechnol 29: 24–26.
64. Rooney I, Butrovich K, Ware CF, (2000) Expression of lymphotoxins and their receptor-Fc fusion proteins by baculovirus. Methods Enzymol 322: 345–363.