Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

MOZ (MYST3, KAT6A) inhibits senescence via the INK4A-ARF pathway

Oncogene volume 34, pages 5807–5820 (2015)Cite this article

Subjects

Abstract

Cellular senescence is an important mechanism that restricts tumour growth. The Ink4a-Arf locus (also known as Cdkn2a), which encodes p16INK4A and p19ARF, has a central role in inducing and maintaining senescence. Given the importance of cellular senescence in restraining tumour growth, great emphasis is being placed on the identification of novel factors that can modulate senescence. The MYST-family histone acetyltransferase MOZ (MYST3, KAT6A), first identified in recurrent translocations in acute myeloid leukaemia, has been implicated in both the promotion and inhibition of senescence. In this study, we investigate the role of MOZ in cellular senescence and show that MOZ is a potent inhibitor of senescence via the INK4A-ARF pathway. Primary mouse embryonic fibroblasts (MEFs) isolated from Moz-deficient embryos exhibit premature senescence, which was rescued on the Ink4a-Arf−/− background. Importantly, senescence resulting from the absence of MOZ was not accompanied by DNA damage, suggesting that MOZ acts independently of the DNA damage response. Consistent with the importance of senescence in cancer, expression profiling revealed that genes overexpressed in aggressive and highly proliferative cancers are expressed at low levels in Moz-deficient MEFs. We show that MOZ is required to maintain normal levels of histone 3 lysine 9 (H3K9) and H3K27 acetylation at the transcriptional start sites of at least four genes, Cdc6, Ezh2, E2f2 and Melk, and normal mRNA levels of these genes. CDC6, EZH2 and E2F2 are known inhibitors of the INK4A-ARF pathway. Using chromatin immunoprecipitation, we show that MOZ occupies the Cdc6, Ezh2 and Melk loci, thereby providing a direct link between MOZ, H3K9 and H3K27 acetylation, and normal transcriptional levels at these loci. This work establishes that MOZ is an upstream inhibitor of the INK4A-ARF pathway, and suggests that inhibiting MOZ may be one way to induce senescence in proliferative tumour cells.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. Borrow J, Stanton VP Jr., Andresen JM, Becher R, Behm FG, Chaganti RS et al. The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein. Nat Genet 1996; 14: 33–41.

    Article  CAS  PubMed  Google Scholar 

  2. Sun T, Wu E . Acute monoblastic leukemia with t(8;16): a distinct clinicopathologic entity; report of a case and review of the literature. Am J Hematol 2001; 66: 207–212.

    Article  CAS  PubMed  Google Scholar 

  3. Stark B, Resnitzky P, Jeison M, Luria D, Blau O, Avigad S et al. A distinct subtype of M4/M5 acute myeloblastic leukemia (AML) associated with t(8:16)(p11:p13), in a patient with the variant t(8:19)(p11:q13)—case report and review of the literature. Leukemia Res 1995; 19: 367–379.

    Article  CAS  Google Scholar 

  4. Haferlach T, Kohlmann A, Klein HU, Ruckert C, Dugas M, Williams PM et al. AML with translocation t(8;16)(p11;p13) demonstrates unique cytomorphological, cytogenetic, molecular and prognostic features. Leukemia 2009; 23: 934–943.

    Article  CAS  PubMed  Google Scholar 

  5. Camos M, Esteve J, Jares P, Colomer D, Rozman M, Villamor N et al. Gene expression profiling of acute myeloid leukemia with translocation t(8;16)(p11;p13) and MYST3-CREBBP rearrangement reveals a distinctive signature with a specific pattern of HOX gene expression. Cancer Res 2006; 66: 6947–6954.

    Article  CAS  PubMed  Google Scholar 

  6. Carapeti M, Aguiar RC, Goldman JM, Cross NC . A novel fusion between MOZ and the nuclear receptor coactivator TIF2 in acute myeloid leukemia. Blood 1998; 91: 3127–3133.

    CAS  PubMed  Google Scholar 

  7. Chaffanet M, Gressin L, Preudhomme C, Soenen-Cornu V, Birnbaum D, Pebusque MJ . MOZ is fused to p300 in an acute monocytic leukemia with t(8;22). Genes Chromosomes Cancer 2000; 28: 138–144.

    Article  CAS  PubMed  Google Scholar 

  8. Esteyries S, Perot C, Adelaide J, Imbert M, Lagarde A, Pautas C et al. NCOA3, a new fusion partner for MOZ/MYST3 in M5 acute myeloid leukemia. Leukemia 2008; 22: 663–665.

    Article  CAS  PubMed  Google Scholar 

  9. Huntly BJ, Shigematsu H, Deguchi K, Lee BH, Mizuno S, Duclos N et al. MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors. Cancer Cell 2004; 6: 587–596.

    Article  CAS  PubMed  Google Scholar 

  10. Thomas T, Corcoran LM, Gugasyan R, Dixon MP, Brodnicki T, Nutt SL et al. Monocytic leukemia zinc finger protein is essential for the development of long-term reconstituting hematopoietic stem cells. Genes Dev 2006; 20: 1175–1186.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Katsumoto T, Aikawa Y, Iwama A, Ueda S, Ichikawa H, Ochiya T et al. MOZ is essential for maintenance of hematopoietic stem cells. Genes Dev 2006; 20: 1321–1330.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Perez-Campo FM, Borrow J, Kouskoff V, Lacaud G . The histone acetyl transferase activity of monocytic leukemia zinc finger is critical for the proliferation of hematopoietic precursors. Blood 2009; 113: 4866–4874.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Voss AK, Collin C, Dixon MP, Thomas T . Moz and retinoic acid coordinately regulate H3K9 acetylation, Hox gene expression, and segment identity. Dev Cell 2009; 17: 674–686.

    Article  CAS  PubMed  Google Scholar 

  14. Voss AK, Vanyai HK, Collin C, Dixon MP, McLennan TS, Sheikh BN et al. MOZ regulates the Tbx1 locus, and Moz mutation partially phenocopies DiGeorge syndrome. Dev Cell 2012; 23: 652–663.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Rokudai S, Aikawa Y, Tagata Y, Tsuchida N, Taya Y, Kitabayashi I . Monocytic leukemia zinc finger (MOZ) interacts with p53 to induce p21 expression and cell-cycle arrest. J Biol Chem 2009; 284: 237–244.

    Article  CAS  PubMed  Google Scholar 

  16. Perez-Campo FM, Costa G, Lie ALM, Stifani S, Kouskoff V, Lacaud G . MOZ-mediated repression of p16 is critical for the self-renewal of neural and hematopoietic stem cells. Stem cells 2013; 32: 1591–1601.

    Article  Google Scholar 

  17. Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA 1995; 92: 9363–9367.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Lu T, Finkel T . Free radicals and senescence. Exp Cell Res 2008; 314: 1918–1922.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Parrinello S, Samper E, Krtolica A, Goldstein J, Melov S, Campisi J . Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts. Nat Cell Biol 2003; 5: 741–747.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM . DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem 1998; 273: 5858–5868.

    Article  CAS  PubMed  Google Scholar 

  21. Muslimovic A, Ismail IH, Gao Y, Hammarsten O . An optimized method for measurement of gamma-H2AX in blood mononuclear and cultured cells. Nat Protocols 2008; 3: 1187–1193.

    Article  CAS  PubMed  Google Scholar 

  22. Liu B, Wang J, Chan KM, Tjia WM, Deng W, Guan X et al. Genomic instability in laminopathy-based premature aging. Nat Med 2005; 11: 780–785.

    Article  CAS  PubMed  Google Scholar 

  23. Tang X, Milyavsky M, Goldfinger N, Rotter V . Amyloid-beta precursor-like protein APLP1 is a novel p53 transcriptional target gene that augments neuroblastoma cell death upon genotoxic stress. Oncogene 2007; 26: 7302–7312.

    Article  CAS  PubMed  Google Scholar 

  24. Vasseur S, Malicet C, Calvo EL, Labrie C, Berthezene P, Dagorn JC et al. Gene expression profiling by DNA microarray analysis in mouse embryonic fibroblasts transformed by rasV12 mutated protein and the E1A oncogene. Mol Cancer 2003; 2: 19.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Ben-Porath I, Thomson MW, Carey VJ, Ge R, Bell GW, Regev A et al. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet 2008; 40: 499–507.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Chiang DY, Villanueva A, Hoshida Y, Peix J, Newell P, Minguez B et al. Focal gains of VEGFA and molecular classification of hepatocellular carcinoma. Cancer Res 2008; 68: 6779–6788.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Sherr CJ . The INK4a/ARF network in tumour suppression. Nat Rev Mol Cell Biol 2001; 2: 731–737.

    Article  CAS  PubMed  Google Scholar 

  28. Besson A, Dowdy SF, Roberts JM . CDK inhibitors: cell cycle regulators and beyond. Dev Cell 2008; 14: 159–169.

    Article  CAS  PubMed  Google Scholar 

  29. Maddika S, Ande SR, Panigrahi S, Paranjothy T, Weglarczyk K, Zuse A et al. Cell survival, cell death and cell cycle pathways are interconnected: implications for cancer therapy. Drug Resist Updat 2007; 10: 13–29.

    Article  CAS  PubMed  Google Scholar 

  30. Serrano M, Lee H, Chin L, Cordon-Cardo C, Beach D, DePinho RA . Role of the INK4a locus in tumor suppression and cell mortality. Cell 1996; 85: 27–37.

    Article  CAS  PubMed  Google Scholar 

  31. Agherbi H, Gaussmann-Wenger A, Verthuy C, Chasson L, Serrano M, Djabali M . Polycomb mediated epigenetic silencing and replication timing at the INK4a/ARF locus during senescence. PloS One 2009; 4: e5622.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Maertens GN, El Messaoudi-Aubert S, Racek T, Stock JK, Nicholls J, Rodriguez-Niedenfuhr M et al. Several distinct polycomb complexes regulate and co-localize on the INK4a tumor suppressor locus. PloS one 2009; 4: e6380.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Dietrich N, Bracken AP, Trinh E, Schjerling CK, Koseki H, Rappsilber J et al. Bypass of senescence by the polycomb group protein CBX8 through direct binding to the INK4A-ARF locus. EMBO J 2007; 26: 1637–1648.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Wu L, Timmers C, Maiti B, Saavedra HI, Sang L, Chong GT et al. The E2F1-3 transcription factors are essential for cellular proliferation. Nature 2001; 414: 457–462.

    Article  CAS  PubMed  Google Scholar 

  35. Uchida F, Uzawa K, Kasamatsu A, Takatori H, Sakamoto Y, Ogawara K et al. Overexpression of CDCA2 in human squamous cell carcinoma: correlation with prevention of G1 phase arrest and apoptosis. PloS One 2013; 8: e56381.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Hayama S, Daigo Y, Yamabuki T, Hirata D, Kato T, Miyamoto M et al. Phosphorylation and activation of cell division cycle associated 8 by aurora kinase B plays a significant role in human lung carcinogenesis. Cancer Res 2007; 67: 4113–4122.

    Article  CAS  PubMed  Google Scholar 

  37. Ohta S, Koide M, Tokuyama T, Yokota N, Nishizawa S, Namba H . Cdc6 expression as a marker of proliferative activity in brain tumors. Oncol Rep 2001; 8: 1063–1066.

    CAS  PubMed  Google Scholar 

  38. Karakaidos P, Taraviras S, Vassiliou LV, Zacharatos P, Kastrinakis NG, Kougiou D et al. Overexpression of the replication licensing regulators hCdt1 and hCdc6 characterizes a subset of non-small-cell lung carcinomas: synergistic effect with mutant p53 on tumor growth and chromosomal instability–evidence of E2F-1 transcriptional control over hCdt1. Am J Pathol 2004; 165: 1351–1365.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Lau E, Zhu C, Abraham RT, Jiang W . The functional role of Cdc6 in S-G2/M in mammalian cells. EMBO Rep 2006; 7: 425–430.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Azzam G, Wang X, Bell D, Murphy ME . CSF1 is a novel p53 target gene whose protein product functions in a feed-forward manner to suppress apoptosis and enhance p53-mediated growth arrest. PloS One 2013; 8: e74297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kig C, Beullens M, Beke L, Van Eynde A, Linders JT, Brehmer D et al. Maternal embryonic leucine zipper kinase (MELK) reduces replication stress in glioblastoma cells. J Biol Chem 2013; 288: 24200–24212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Bornstein G, Bloom J, Sitry-Shevah D, Nakayama K, Pagano M, Hershko A . Role of the SCFSkp2 ubiquitin ligase in the degradation of p21Cip1 in S phase. J Biol Chem 2003; 278: 25752–25757.

    Article  CAS  PubMed  Google Scholar 

  43. Carrano AC, Eytan E, Hershko A, Pagano M . SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27. Nat Cell Biol 1999; 1: 193–199.

    Article  CAS  PubMed  Google Scholar 

  44. Kamura T, Hara T, Kotoshiba S, Yada M, Ishida N, Imaki H et al. Degradation of p57Kip2 mediated by SCFSkp2-dependent ubiquitylation. Proc Natl Acad Sci USA 2003; 100: 10231–10236.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Jaffe JD, Wang Y, Chan HM, Zhang J, Huether R, Kryukov GV et al. Global chromatin profiling reveals NSD2 mutations in pediatric acute lymphoblastic leukemia. Nat Genet 2013; 45: 1386–1391.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Reimann M, Lee S, Loddenkemper C, Dorr JR, Tabor V, Aichele P et al. Tumor stroma-derived TGF-beta limits myc-driven lymphomagenesis via Suv39h1-dependent senescence. Cancer Cell 2010; 17: 262–272.

    Article  CAS  PubMed  Google Scholar 

  47. Chen Z, Trotman LC, Shaffer D, Lin HK, Dotan ZA, Niki M et al. Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature 2005; 436: 725–730.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Braig M, Lee S, Loddenkemper C, Rudolph C, Peters AH, Schlegelberger B et al. Oncogene-induced senescence as an initial barrier in lymphoma development. Nature 2005; 436: 660–665.

    Article  CAS  PubMed  Google Scholar 

  49. Kamb A, Gruis NA, Weaver-Feldhaus J, Liu Q, Harshman K, Tavtigian SV et al. A cell cycle regulator potentially involved in genesis of many tumor types. Science 1994; 264: 436–440.

    Article  CAS  PubMed  Google Scholar 

  50. Quelle DE, Zindy F, Ashmun RA, Sherr CJ . Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest. Cell 1995; 83: 993–1000.

    Article  CAS  PubMed  Google Scholar 

  51. Serrano M, Hannon GJ, Beach D . A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 1993; 366: 704–707.

    Article  CAS  PubMed  Google Scholar 

  52. Koh J, Enders GH, Dynlacht BD, Harlow E . Tumour-derived p16 alleles encoding proteins defective in cell-cycle inhibition. Nature 1995; 375: 506–510.

    Article  CAS  PubMed  Google Scholar 

  53. Weber JD, Taylor LJ, Roussel MF, Sherr CJ, Bar-Sagi D . Nucleolar Arf sequesters Mdm2 and activates p53. Nat Cell Biol 1999; 1: 20–26.

    Article  CAS  PubMed  Google Scholar 

  54. Bachmann IM, Halvorsen OJ, Collett K, Stefansson IM, Straume O, Haukaas SA et al. EZH2 expression is associated with high proliferation rate and aggressive tumor subgroups in cutaneous melanoma and cancers of the endometrium, prostate, and breast. J Clin Oncol 2006; 24: 268–273.

    Article  CAS  PubMed  Google Scholar 

  55. Kleer CG, Cao Q, Varambally S, Shen R, Ota I, Tomlins SA et al. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci USA 2003; 100: 11606–11611.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 2002; 419: 624–629.

    Article  CAS  PubMed  Google Scholar 

  57. Chen HZ, Tsai SY, Leone G . Emerging roles of E2Fs in cancer: an exit from cell cycle control. Nat Rev Cancer 2009; 9: 785–797.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Gonzalez S, Klatt P, Delgado S, Conde E, Lopez-Rios F, Sanchez-Cespedes M et al. Oncogenic activity of Cdc6 through repression of the INK4/ARF locus. Nature 2006; 440: 702–706.

    Article  CAS  PubMed  Google Scholar 

  59. Yan Z, DeGregori J, Shohet R, Leone G, Stillman B, Nevins JR et al. Cdc6 is regulated by E2F and is essential for DNA replication in mammalian cells. Proc Natl Acad Sci USA 1998; 95: 3603–3608.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Bracken AP, Pasini D, Capra M, Prosperini E, Colli E, Helin K . EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer. EMBO J 2003; 22: 5323–5335.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Nakano I, Paucar AA, Bajpai R, Dougherty JD, Zewail A, Kelly TK et al. Maternal embryonic leucine zipper kinase (MELK) regulates multipotent neural progenitor proliferation. J Cell Biol 2005; 170: 413–427.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Nakano I, Masterman-Smith M, Saigusa K, Paucar AA, Horvath S, Shoemaker L et al. Maternal embryonic leucine zipper kinase is a key regulator of the proliferation of malignant brain tumors, including brain tumor stem cells. J Neurosci Res 2008; 86: 48–60.

    Article  CAS  PubMed  Google Scholar 

  63. Rokudai S, Laptenko O, Arnal SM, Taya Y, Kitabayashi I, Prives C . MOZ increases p53 acetylation and premature senescence through its complex formation with PML. Proc Natl Acad Sci USA 2013; 110: 3895–3900.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Champagne N, Pelletier N, Yang XJ . The monocytic leukemia zinc finger protein MOZ is a histone acetyltransferase. Oncogene 2001; 20: 404–409.

    Article  CAS  PubMed  Google Scholar 

  65. Doyon Y, Cayrou C, Ullah M, Landry AJ, Cote V, Selleck W et al. ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation. Mol Cell 2006; 21: 51–64.

    Article  CAS  PubMed  Google Scholar 

  66. Schwickert TA, Tagoh H, Gultekin S, Dakic A, Axelsson E, Minnich M et al. Stage-specific control of early B cell development by the transcription factor Ikaros. Nat Immunol 2014; 15: 283–293.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Voss AK, Thomas T, Gruss P . Efficiency assessment of the gene trap approach. Dev Dynamics 1998; 212: 171–180.

    Article  CAS  Google Scholar 

  68. Debacq-Chainiaux F, Erusalimsky JD, Campisi J, Toussaint O . Protocols to detect senescence-associated beta-galactosidase (SA-betagal) activity, a biomarker of senescent cells in culture and in vivo. Nat Protocols 2009; 4: 1798–1806.

    Article  CAS  PubMed  Google Scholar 

  69. Shi W, Oshlack A, Smyth GK . Optimizing the noise versus bias trade-off for Illumina whole genome expression BeadChips. Nucleic Acids Res 2010; 38: e204.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Smyth GK . Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 2004; 3: Article3.

    Article  PubMed  Google Scholar 

  71. Wu D, Smyth GK . Camera: a competitive gene set test accounting for inter-gene correlation. Nucleic Acids Res 2012; 40: e133.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Liberzon A, Subramanian A, Pinchback R, Thorvaldsdottir H, Tamayo P, Mesirov JP . Molecular signatures database (MSigDB) 3.0. Bioinformatics 2011; 27: 1739–1740.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Wu D, Lim E, Vaillant F, Asselin-Labat ML, Visvader JE, Smyth GK . ROAST: rotation gene set tests for complex microarray experiments. Bioinformatics 2010; 26: 2176–2182.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Wu Z, Irizarry R, Gentleman R, Martinez-Murillo F, Spencer F . A model-based background adjustment for oligonucleotide expression arrays. J Am Stat Assoc 2004; 99: 909.

    Article  Google Scholar 

  75. Voss AK, Dixon MP, McLennan T, Kueh AJ, Thomas T . Chromatin immunoprecipitation of mouse embryos. Methods Mol Biol 2012; 809: 335–352.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Carmen Gatt and Faye Dabrowski for technical support. We thank Andreas Strasser for helpful discussions and Liz Valente for the provision of the anti-p21CIP1 antibody. This work was supported by the Australian National Health and Medical Research Council (senior research fellowships to AKV and TT; scholarship to BNS), the Australian Mitochondrial Disease Foundation (MJB), Australian Postgraduate Awards (to MJB, FE and HKV) and operational infrastructure grants from the Australian Federal Government (IRISS) and the Victorian State Government (OIS).

Author information

Author notes

  1. A K Voss and T Thomas: These authors co-supervised this project and contributed equally.

Authors and Affiliations

  1. Division of Development and Cancer, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia

    B N Sheikh, F El-Saafin, H K Vanyai, N L Downer, A J Kueh, R E May, A K Voss & T Thomas

  2. Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia,

    B N Sheikh, F El-Saafin, H K Vanyai, A K Voss & T Thomas

  3. Division of Bioinformatics, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia

    B Phipson & G K Smyth

  4. Murdoch Children’s Research Institute, Melbourne, Victoria, Australia

    B Phipson & M J Bird

  5. Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia

    M J Bird

  6. Department of Mathematics and Statistics, University of Melbourne, Melbourne, Victoria, Australia

    G K Smyth

Authors
  1. B N Sheikh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B Phipson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F El-Saafin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H K Vanyai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N L Downer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M J Bird
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A J Kueh
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. R E May
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. G K Smyth
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. A K Voss
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. T Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to A K Voss or T Thomas.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on the Oncogene website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sheikh, B., Phipson, B., El-Saafin, F. et al. MOZ (MYST3, KAT6A) inhibits senescence via the INK4A-ARF pathway. Oncogene 34, 5807–5820 (2015). https://doi.org/10.1038/onc.2015.33

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/onc.2015.33

This article is cited by

Search

Advanced search

Quick links