Sustained activation of NF-κB through constitutively active IKKβ leads to senescence bypass in murine dermal fibroblasts

References

• Furman D, Campisi J, Verdin E, et al. Chronic inflammation in the etiology of disease across the life span. Nat Med. 2019;25(12):1822–32. doi: 10.1038/s41591-019-0675-0
   PubMed Web of Science ®Google Scholar
• Liu T, Zhang L, Joo D, et al. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2(1):17023–. doi: 10.1038/sigtrans.2017.23
   PubMed Web of Science ®Google Scholar
• Hayden M, Ghosh S. NF-κB, the first quarter-century: remarkable progress and outstanding questions. Genes Dev. 2012;26(3):203–34. doi: 10.1101/gad.183434.111
   PubMed Web of Science ®Google Scholar
• Sun SC. Non-canonical NF-κB signaling pathway. Cell Res. 2011;21(1):71–85. doi: 10.1038/cr.2010.177
   PubMed Web of Science ®Google Scholar
• Hinz M, Scheidereit C. The IκB kinase complex in NF-κB regulation and beyond. EMBO Rep. 2014;15(1):46–61. doi: 10.1002/embr.201337983
   PubMed Web of Science ®Google Scholar
• Prescott JA, Balmanno K, Mitchell JP, et al. IKKα plays a major role in canonical NF-κB signalling in colorectal cells. Biochem J. 2022;479(3):305–25. doi: 10.1042/BCJ20210783
   PubMed Web of Science ®Google Scholar
• Solt L, Madge L, Orange J, et al. Interleukin-1-induced NF-κB activation is NEMO-dependent but does not require IKKβ. J Biol Chem. 2007;282(12):8724–8733. doi: 10.1074/jbc.M609613200
   PubMed Web of Science ®Google Scholar
• Osorio F, Soria-Valles C, Santiago-Fernández O, et al. NF-κB signaling as a driver of ageing. Int Rev Cell Mol Biol. 2016;326:133–174.
   PubMed Web of Science ®Google Scholar
• Tilstra JS, Robinson AR, Wang J, et al. NF-κB inhibition delays DNA damage–induced senescence and aging in mice. J Clin Invest. 2012;122(7):2601–2612. doi: 10.1172/JCI45785
   PubMed Web of Science ®Google Scholar
• Kawahara TL, Michishita E, Adler AS, et al. SIRT6 links histone H3 lysine 9 deacetylation to NF-κB-dependent gene expression and organismal life span. Cell. 2009;136(1):62–74. doi: 10.1016/j.cell.2008.10.052
   PubMed Web of Science ®Google Scholar
• Adler AS, Sinha S, Kawahara TL, et al. Motif module map reveals enforcement of aging by continual NF-κB activity. Genes Dev. 2007;21(24):3244–3257. doi: 10.1101/gad.1588507
   PubMed Web of Science ®Google Scholar
• Osorio F, Bárcena C, Soria-Valles C, et al. Nuclear lamina defects cause ATM-dependent NF-κB activation and link accelerated aging to a systemic inflammatory response. Genes Dev. 2012;26(20):2311–24. doi: 10.1101/gad.197954.112
   PubMed Web of Science ®Google Scholar
• Zhang L, Zhao J, Mu X, et al. Novel small molecule inhibition of IKK/NF-κB activation reduces markers of senescence and improves healthspan in mouse models of aging. Aging Cell. 2021;20(12):e13486. doi: 10.1111/acel.13486
   PubMed Web of Science ®Google Scholar
• Jurk D, Wilson C, Passos J, et al. Chronic inflammation induces telomere dysfunction and accelerates ageing in mice. Nat Commun. 2014;5(1). doi: 10.1038/ncomms5172
   PubMedGoogle Scholar
• Bernal GM, Wahlstrom JS, Crawley CD, et al. Loss of Nfkb1 leads to early onset aging. Aging (Albany NY). 2014;6(11):931–943. doi: 10.18632/aging.100702
   PubMedGoogle Scholar
• Salminen A, Kauppinen A, Kaarniranta K. Emerging role of NF-κB signaling in the induction of senescence-associated secretory phenotype (SASP). Cell Signal. 2012;24(4):835–45. doi: 10.1016/j.cellsig.2011.12.006
   PubMed Web of Science ®Google Scholar
• Rodier F, Campisi J. Four faces of cellular senescence. J Cell Bio. 2011;192(4):547–56. doi: 10.1083/jcb.201009094
   PubMed Web of Science ®Google Scholar
• Hernandez-Segura A, Nehme J, Demaria M. Hallmarks of cellular senescence. Trends Cell Biol. 2018;28(6):436–53. doi: 10.1016/j.tcb.2018.02.001
   PubMed Web of Science ®Google Scholar
• Paramos-de-Carvalho D, Jacinto A, Saúde L. The right time for senescence. Elife. 2021;10:10. doi: 10.7554/eLife.72449
   Web of Science ®Google Scholar
• Birch J, Gil J. Senescence and the SASP: many therapeutic avenues. Genes Dev. 2020;34(23–24):1565–76. doi: 10.1101/gad.343129.120
   PubMed Web of Science ®Google Scholar
• McHugh D, Gil J. Senescence and aging: Causes, consequences, and therapeutic avenues. J Cell Bio. 2018;217(1):65–77. doi: 10.1083/jcb.201708092
   PubMed Web of Science ®Google Scholar
• Baker DJ, Childs BG, Durik M, et al. Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature. 2016;530(7589):184–189. doi: 10.1038/nature16932
   PubMed Web of Science ®Google Scholar
• Xu M, Pirtskhalava T, Farr J, et al. Senolytics improve physical function and increase lifespan in old age. Nature Med. 2018;24(8):1246–56. doi: 10.1038/s41591-018-0092-9
   PubMed Web of Science ®Google Scholar
• Rovillain E, Mansfield L, Caetano C, et al. Activation of nuclear factor-kappa B signalling promotes cellular senescence. Oncogene. 2011;30(20):2356–66. doi: 10.1038/onc.2010.611
   PubMed Web of Science ®Google Scholar
• Chien Y, Scuoppo C, Wang X, et al. Control of the senescence-associated secretory phenotype by NF-κB promotes senescence and enhances chemosensitivity. Genes Dev. 2011;25(20):2125–36. doi: 10.1101/gad.17276711
   PubMed Web of Science ®Google Scholar
• Seitz CS, Deng H, Hinata K, et al. Nuclear factor kappaB subunits induce epithelial cell growth arrest. Cancer Res. 2000;60(15):4085–4092.
   PubMed Web of Science ®Google Scholar
• Bernard D, Gosselin K, Monte D, et al. Involvement of Rel/nuclear factor-κB transcription factors in keratinocyte senescence. Cancer Res. 2004;64(2):472–481. doi: 10.1158/0008-5472.CAN-03-0005
   PubMed Web of Science ®Google Scholar
• Bu Y, Li X, He Y, et al. A phosphomimetic mutant of RelA/p65 at Ser536 induces apoptosis and senescence: an implication for tumor-suppressive role of Ser536 phosphorylation. Int J Cancer. 2016;138(5):1186–98. doi: 10.1002/ijc.29852
   PubMed Web of Science ®Google Scholar
• Bernal GM, Wu L, Voce DJ, et al. p52 signaling promotes cellular senescence. Cell Biosci. 2022;12(1):43. doi: 10.1186/s13578-022-00779-6
   PubMed Web of Science ®Google Scholar
• De Donatis G, Le Pape E, Pierron A, et al. NF-kB2 induces senescence bypass in melanoma via a direct transcriptional activation of EZH2. Oncogene. 2016;35(21):2735–45. doi: 10.1038/onc.2015.331
   PubMed Web of Science ®Google Scholar
• Batsi C, Markopoulou S, Vartholomatos G, et al. Chronic NF-κB activation delays RasV12-induced premature senescence of human fibroblasts by suppressing the DNA damage checkpoint response. Mech Ageing Dev. 2009;130(7):409–419. doi: 10.1016/j.mad.2009.04.002
   PubMed Web of Science ®Google Scholar
• Iannetti A, Ledoux AC, Tudhope SJ, et al. Regulation of p53 and Rb links the alternative NF-κB pathway to EZH2 expression and cell senescence. PloS Genet. 2014;10(9):e1004642. doi: 10.1371/journal.pgen.1004642
   PubMed Web of Science ®Google Scholar
• Wang J, Jacob NK, Ladner KJ, et al. RelA/p65 functions to maintain cellular senescence by regulating genomic stability and DNA repair. EMBO Rep. 2009;10(11):1272–1278. doi: 10.1038/embor.2009.197
   PubMed Web of Science ®Google Scholar
• Hinata K, Gervin AM, Jennifer Zhang Y, et al. Divergent gene regulation and growth effects by NF-κB in epithelial and mesenchymal cells of human skin. Oncogene. 2003;22(13):1955–1964. doi: 10.1038/sj.onc.1206198
   PubMed Web of Science ®Google Scholar
• Zhang S, Harada M, Kimura T, et al. Deletion of IKKβ in activated fibroblasts promotes tumor progression in melanoma. Biochem Biophys Res Commun. 2022;621:46–52. doi: 10.1016/j.bbrc.2022.07.004
   PubMed Web of Science ®Google Scholar
• Sasaki Y, Derudder E, Hobeika E, et al. Canonical NF-κB activity, dispensable for B cell development, replaces BAFF-Receptor signals and promotes B cell proliferation upon activation. Immunity. 2006;24(6):729–739. doi: 10.1016/j.immuni.2006.04.005
   PubMed Web of Science ®Google Scholar
• Boucher P, Gotthardt M, Li WP, et al. LRP: role in vascular wall integrity and protection from atherosclerosis. Science. 2003;300(5617):329–332. doi: 10.1126/science.1082095
   PubMed Web of Science ®Google Scholar
• Muzumdar MD, Tasic B, Miyamichi K, et al. A global double-fluorescent cre reporter mouse. Genesis. 2007;45(9):593–605. doi: 10.1002/dvg.20335
   PubMed Web of Science ®Google Scholar
• Li ZW, Omori SA, Labuda T, et al. IKKβ is required for peripheral B cell survival and proliferation. J Immunol. 2003;170(9):4630–4637. doi: 10.4049/jimmunol.170.9.4630
   PubMed Web of Science ®Google Scholar
• Al-Huseini I, Ashida N, Kimura T. Deletion of IκB-Kinase β in smooth muscle cells induces vascular calcification through β-Catenin–Runt-related transcription factor 2 signaling. J Am Heart Assoc. 2018;7(1). doi: 10.1161/JAHA.117.007405
   PubMed Web of Science ®Google Scholar
• Al-Huseini I, Harada M, Nishi K, et al. Improvement of insulin signalling rescues inflammatory cardiac dysfunction. Sci Rep. 2019;9(1):14801. doi: 10.1038/s41598-019-51304-8
   PubMedGoogle Scholar
• Meylan E, Dooley AL, Feldser DM, et al. Requirement for NF-κB signalling in a mouse model of lung adenocarcinoma. Nature. 2009;462(7269):104–107. doi: 10.1038/nature08462
   PubMed Web of Science ®Google Scholar
• Xie F, Xiao P, Chen D, et al. miRdeepfinder: a miRNA analysis tool for deep sequencing of plant small RNAs. Plant Mol Biol. 2012;80(1):75–84. doi: 10.1007/s11103-012-9885-2
   Web of Science ®Google Scholar
• Hernandez-Segura A, Rubingh R, Demaria M. Identification of stable senescence-associated reference genes. Aging Cell. 2019;18(2):e12911. doi: 10.1111/acel.12911
   PubMed Web of Science ®Google Scholar
• Assinder SJ, Stanton JA, Prasad PD. Transgelin: an actin-binding protein and tumour suppressor. Int J Biochem Cell Biol. 2009;41(3):482–486. doi: 10.1016/j.biocel.2008.02.011
   PubMed Web of Science ®Google Scholar
• Sakurai H, Chiba H, Miyoshi H, et al. IκB kinases phosphorylate NF-κB p65 subunit on serine 536 in the transactivation domain. J Biol Chem. 1999;274(43):30353–30356. doi: 10.1074/jbc.274.43.30353
   PubMed Web of Science ®Google Scholar
• Parrinello S, Samper E, Krtolica A, et al. Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts. Nat Cell Biol. 2003;5(8):741–7. doi: 10.1038/ncb1024
   PubMed Web of Science ®Google Scholar
• Woo R, Poon R. Activated oncogenes promote and cooperate with chromosomal instability for neoplastic transformation. Genes Dev. 2004;18(11):1317–30. doi: 10.1101/gad.1165204
   PubMed Web of Science ®Google Scholar
• Coppé J, Patil C, Rodier F, et al. A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen. PloS One. 2010;5(2):e9188. doi: 10.1371/journal.pone.0009188
   PubMed Web of Science ®Google Scholar
• Bhatt D, Ghosh S. Regulation of the NF-κB-Mediated transcription of inflammatory genes. Front Immunol. 2014;5:71. doi: 10.3389/fimmu.2014.00071
   PubMed Web of Science ®Google Scholar
• Antonia RJ, Hagan RS, Baldwin AS. Expanding the view of IKK: new substrates and new biology. Trends Cell Biol. 2021;31(3):166–78. doi: 10.1016/j.tcb.2020.12.003
   PubMed Web of Science ®Google Scholar
• Xia Y, Padre R, De Mendoza T, et al. Phosphorylation of p53 by IkappaB kinase 2 promotes its degradation by beta-TrCP. Proc Natl Acad Sci U S A. 2009;106:2629–2634. doi: 10.1073/pnas.0812256106
   Google Scholar
• Guo Y, Yuan C, Weghorst C, et al. IKKβ specifically binds to P16 and phosphorylates Ser8 of P16. Biochem Biophys Res Commun. 2010;393(3):504–508. doi: 10.1016/j.bbrc.2010.02.035
   PubMed Web of Science ®Google Scholar
• Liao JM, Zhang Y, Liao W, et al. IκB kinase β (IKKβ) inhibits p63 isoform γ (TAp63γ) transcriptional activity. J Biol Chem. 2013;288(25):18184–93. doi: 10.1074/jbc.M113.466540
   PubMed Web of Science ®Google Scholar
• Wang CY, Mayo MW, Baldwin AS. TNF- and cancer therapy-induced apoptosis: potentiation by inhibition of NF-κB. Science. 1996;274(5288):784–787. doi: 10.1126/science.274.5288.784
   PubMed Web of Science ®Google Scholar
• Tasdemir N, Lowe SW. Senescent cells spread the word: non-cell autonomous propagation of cellular senescence. EMBO J. 2013;32(14):1975–6. doi: 10.1038/emboj.2013.139
   PubMed Web of Science ®Google Scholar
• Salminen A, Kaarniranta K. Control of p53 and NF-κB signaling by WIP1 and MIF: role in cellular senescence and organismal aging. Cell Signal. 2011;23(5):747–52. doi: 10.1016/j.cellsig.2010.10.012
   PubMed Web of Science ®Google Scholar
• Hudson JD, Shoaibi MA, Maestro R, et al. A proinflammatory cytokine inhibits p53 tumor suppressor activity. J Exp Med. 1999;190(10):1375–82. doi: 10.1084/jem.190.10.1375
   PubMed Web of Science ®Google Scholar
• Itahana K, Campisi J, Dimri G. Mechanisms of cellular senescence in human and mouse cells. Biogerontology. 2004;5(1):1–10. doi: 10.1023/B:BGEN.0000017682.96395.10
   PubMed Web of Science ®Google Scholar
• Odell A, Askham J, Whibley C, et al. How to become immortal: let MEFs count the ways. Aging (Albany NY). 2010;2(3):160–5. doi: 10.18632/aging.100129
   PubMedGoogle Scholar
• Krones-Herzig A, Adamson E, Mercola D. Early growth response 1 protein, an upstream gatekeeper of the p53 tumor suppressor, controls replicative senescence. Proc Natl Acad Sci U S A. 2003;100(6):3233–8. doi: 10.1073/pnas.2628034100
   PubMed Web of Science ®Google Scholar
• Chua KF, Mostoslavsky R, Lombard DB, et al. Mammalian SIRT1 limits replicative life span in response to chronic genotoxic stress. Cell Metab. 2005;2(1):67–76. doi: 10.1016/j.cmet.2005.06.007
   PubMed Web of Science ®Google Scholar
• Takeuchi S, Takahashi A, Motoi N, et al. Intrinsic cooperation between p16INK4a and p21Waf1/Cip1 in the onset of cellular senescence and tumor suppression in vivo. Cancer Res. 2010;70(22):9381–90. doi: 10.1158/0008-5472.CAN-10-0801
   PubMed Web of Science ®Google Scholar
• Carbone CJ, Graña X, Reddy EP, et al. p21 loss cooperates with INK4 inactivation facilitating immortalization and bcl-2 –mediated anchorage-independent growth of oncogene-transduced primary mouse fibroblasts. Cancer Res. 2007;67(9):4130–4137. doi: 10.1158/0008-5472.CAN-07-0499
   PubMed Web of Science ®Google Scholar
• Kortlever RM, Higgins PJ, Bernards R. Plasminogen activator inhibitor-1 is a critical downstream target of p53 in the induction of replicative senescence. Nat Cell Biol. 2006;8(8):877–84. doi: 10.1038/ncb1448
   PubMed Web of Science ®Google Scholar
• Wu H, Lozano G. NF-kappa B activation of p53. A potential mechanism for suppressing cell growth in response to stress. J Biol Chem. 1994;269(31):20067–74. doi: 10.1016/S0021-9258(17)32128-2
   PubMed Web of Science ®Google Scholar
• Liu Y, Tavana O, Gu W. p53 modifications: exquisite decorations of the powerful guardian. J Mol Cell Biol. 2019;11(7):564–577. doi: 10.1093/jmcb/mjz060
   PubMed Web of Science ®Google Scholar
• TODARO G, GREEN H. Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines. J Cell Bio. 1963;17(2):299–313. doi: 10.1083/jcb.17.2.299
   PubMed Web of Science ®Google Scholar
• Harvey D, Levine A. p53 alteration is a common event in the spontaneous immortalization of primary BALB/c murine embryo fibroblasts. Genes Dev. 1991;5(12b):2375–85. doi: 10.1101/gad.5.12b.2375
   PubMed Web of Science ®Google Scholar
• Brugarolas J, Moberg K, Boyd SD, et al. Inhibition of cyclin-dependent kinase 2 by p21 is necessary for retinoblastoma protein-mediated G 1 arrest after γ-irradiation. Proc Natl Acad Sci U S A. 1999;96(3):1002–1007. doi: 10.1073/pnas.96.3.1002
   PubMed Web of Science ®Google Scholar
• Gil J, Peters G. Regulation of the INK4b–ARF–INK4a tumour suppressor locus: all for one or one for all. Nat Rev Mol Cell Biol. 2006;7(9):667–677. doi: 10.1038/nrm1987
   PubMed Web of Science ®Google Scholar
• Kamijo T, Zindy F, Roussel M, et al. Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF. Cell. 1997;91(5):649–59. doi: 10.1016/S0092-8674(00)80452-3
   PubMed Web of Science ®Google Scholar
• Sharpless N, Bardeesy N, Lee K, et al. Loss of p16Ink4a with retention of p19Arf predisposes mice to tumorigenesis. Nature. 2001;413(6851):86–91. doi: 10.1038/35092592
   PubMed Web of Science ®Google Scholar
• Farooq U, Notani D. Transcriptional regulation of INK4/ARF locus by cis and trans mechanisms. Front Cell Dev Biol. 2022;10:948351. doi: 10.3389/fcell.2022.948351
   PubMed Web of Science ®Google Scholar
• Bracken AP, Kleine-Kohlbrecher D, Dietrich N, et al. The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. Genes Dev. 2007;21(5):525–30. doi: 10.1101/gad.415507
   PubMed Web of Science ®Google Scholar
• Kamminga LM, Bystrykh LV, de Boer A, et al. The Polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion. Blood. 2006;107(5):2170–9. doi: 10.1182/blood-2005-09-3585
   PubMed Web of Science ®Google Scholar
• Tzatsos A, Pfau R, Kampranis SC, et al. Ndy1/KDM2B immortalizes mouse embryonic fibroblasts by repressing the Ink4a/Arf locus. Proc Natl Acad Sci U S A. 2009;106(8):2641–6. doi: 10.1073/pnas.0813139106
   PubMed Web of Science ®Google Scholar
• Dietrich N, Bracken AP, Trinh E, et al. Bypass of senescence by the polycomb group protein CBX8 through direct binding to the INK4A-ARF locus. EMBO J. 2007;26(6):1637–48. doi: 10.1038/sj.emboj.7601632
   PubMed Web of Science ®Google Scholar
• Jacobs JJ, Kieboom K, Marino S, et al. The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus. Nature. 1999;397(6715):164–168. doi: 10.1038/16476
   PubMed Web of Science ®Google Scholar
• Penzo M, Massa PE, Olivotto E, et al. Sustained NF-κB activation produces a short-term cell proliferation block in conjunction with repressing effectors of cell cycle progression controlled by E2F or FoxM1. J Cell Physiol. 2009;218(1):215–227. doi: 10.1002/jcp.21596
   PubMed Web of Science ®Google Scholar
• Araki K, Kawauchi K, Tanaka N. IKK/NF-κB signaling pathway inhibits cell-cycle progression by a novel Rb-independent suppression system for E2F transcription factors. Oncogene. 2008;27(43):5696–5705. doi: 10.1038/onc.2008.184
   PubMed Web of Science ®Google Scholar
• Li J, Joo SH, Tsai MD. An NF-κB-Specific Inhibitor, IκBα, binds to and inhibits cyclin-dependent kinase 4. Biochemistry. 2003;42(46):13476–13483. doi: 10.1021/bi035390r
   PubMed Web of Science ®Google Scholar
• Deng Q, Liao R, Wu BL, et al. High intensity ras signaling induces premature senescence by activating p38 pathway in primary human fibroblasts. J Biol Chem. 2004;279(2):1050–9. doi: 10.1074/jbc.M308644200
   PubMed Web of Science ®Google Scholar
• Morgan MJ, Liu ZG. Crosstalk of reactive oxygen species and NF-κB signaling. Cell Res. 2011;21(1):103–15. doi: 10.1038/cr.2010.178
   PubMed Web of Science ®Google Scholar
• Tang RH, Zheng XL, Callis TE, et al. Myocardin inhibits cellular proliferation by inhibiting NF-κB(p65)-dependent cell cycle progression. Proc Natl Acad Sci U S A. 2008;105(9):3362–3367. doi: 10.1073/pnas.0705842105
   PubMed Web of Science ®Google Scholar
• Guo X, Hong S, He H, et al. NFκB promotes oxidative stress-induced necrosis and ischemia/reperfusion injury by inhibiting Nrf2-ARE pathway. Free Radic Biol Med. 2020;159:125–35. doi: 10.1016/j.freeradbiomed.2020.07.031
   PubMed Web of Science ®Google Scholar
• Webster GA, Perkins ND. Transcriptional cross talk between NF-κB and p53. Mol Cell Biol. 1999;19(5):3485–3495. doi: 10.1128/MCB.19.5.3485
   PubMed Web of Science ®Google Scholar
• Wadgaonkar R, Phelps KM, Haque Z, et al. CREB-binding protein is a nuclear integrator of nuclear factor-κB and p53 signaling. J Biol Chem. 1999;274(4):1879–1882. doi: 10.1074/jbc.274.4.1879
   PubMed Web of Science ®Google Scholar
• Gudkov AV, Komarova EA. p53 and the carcinogenicity of chronic inflammation. Cold Spring Harb Perspect Med. 2016;6(11):6. doi: 10.1101/cshperspect.a026161
   Web of Science ®Google Scholar
• Tergaonkar V, Pando M, Vafa O, et al. p53 stabilization is decreased upon NFκB activation. Cancer Cell. 2002;1(5):493–503. doi: 10.1016/S1535-6108(02)00068-5
   PubMed Web of Science ®Google Scholar
• Bren GD, Solan NJ, Miyoshi H, et al. Transcription of the RelB gene is regulated by NF-kappaB. Oncogene. 2001;20:7722–7733. doi: 10.1038/sj.onc.1204868
   PubMed Web of Science ®Google Scholar
• Lombardi L, Ciana P, Cappellini C, et al. Structural and functional characterization of the promoter regions of the NFKB2 gene. Nucleic Acids Res. 1995;23(12):2328–36. doi: 10.1093/nar/23.12.2328
   PubMed Web of Science ®Google Scholar
• Tzatsos A, Paskaleva P, Lymperi S, et al. 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. 2011;286(38):33061–9. doi: 10.1074/jbc.M111.257667
   PubMed Web of Science ®Google Scholar
• Cakouros D, Isenmann S, Cooper L, et al. Twist-1 induces Ezh2 recruitment regulating histone methylation along the Ink4A/Arf locus in mesenchymal stem cells. Mol Cell Biol. 2012;32(8):1433–41. doi: 10.1128/MCB.06315-11
   PubMed Web of Science ®Google Scholar
• Sander S, Bullinger L, Klapproth K, et al. MYC stimulates EZH2 expression by repression of its negative regulator miR-26a. Blood. 2008;112:4202–4212. doi: 10.1182/blood-2008-03-147645
   PubMed Web of Science ®Google Scholar
• Sheikh BN, Phipson B, El-Saafin F, et al. MOZ (MYST3, KAT6A) inhibits senescence via the INK4A-ARF pathway. Oncogene. 2015;34(47):5807–20. doi: 10.1038/onc.2015.33
   PubMed Web of Science ®Google Scholar
• Wilson BG, Wang X, Shen X, et al. Epigenetic antagonism between polycomb and SWI/SNF complexes during oncogenic transformation. Cancer Cell. 2010;18(4):316–328. doi: 10.1016/j.ccr.2010.09.006
   PubMed Web of Science ®Google Scholar
• Ge R, Wang Z, Zeng Q, et al. F-box protein 10, an NF-κB-dependent anti-apoptotic protein, regulates TRAIL-induced apoptosis through modulating c-Fos/c-FLIP pathway. Cell Death Differ. 2011;18(7):1184–95. doi: 10.1038/cdd.2010.185
   PubMed Web of Science ®Google Scholar
• Pham CG, Bubici C, Zazzeroni F, et al. Upregulation of twist-1 by NF-kappaB blocks cytotoxicity induced by chemotherapeutic drugs. Mol Cell Biol. 2007;27:3920–3935. doi: 10.1128/MCB.01219-06
   PubMed Web of Science ®Google Scholar
• Duyao MP, Buckler AJ, Sonenshein GE. Interaction of an NF-kappa B-like factor with a site upstream of the c-myc promoter. Proc Natl Acad Sci U S A. 1990;87(12):4727–31. doi: 10.1073/pnas.87.12.4727
   PubMed Web of Science ®Google Scholar
• Bracken AP, Pasini D, Capra M, et al. EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer. EMBO J. 2003;22(20):5323–5335. doi: 10.1093/emboj/cdg542
   PubMed Web of Science ®Google Scholar
• McCabe MT, Ott HM, Ganji G, et al. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature. 2012;492(7427):108–112. doi: 10.1038/nature11606
   PubMed Web of Science ®Google Scholar
• Piunti A, Rossi A, Cerutti A, et al. Polycomb proteins control proliferation and transformation independently of cell cycle checkpoints by regulating DNA replication. Nat Commun. 2014;5(1):3649. doi: 10.1038/ncomms4649
   PubMedGoogle Scholar
• Ledoux AC, Perkins ND. NF-κB and the cell cycle. Biochem Soc Trans. 2014;42(1):76–81. doi: 10.1042/BST20130156
   PubMedGoogle Scholar
• Sherr CJ, Roberts JM. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 1999;13(12):1501–12. doi: 10.1101/gad.13.12.1501
   PubMed Web of Science ®Google Scholar