Polycomb complexes regulate cellular senescence by repression of ARF in cooperation with E2F3 - PubMed

Polycomb complexes regulate cellular senescence by repression of ARF in cooperation with E2F3

Jun Miki et al. Genes Cells. 2007 Dec.

Free article

Abstract

Cellular senescence is a program in normal cells triggered in response to various types of stress that cells experience when they are explanted into culture. In this study, functional analyses on the role of the class II polycomb complex in cellular senescence were performed using mouse embryo fibroblasts (MEFs) with a genetically deleted member of the complex, Mel18. Mel18-null MEFs undergo typical premature senescence accompanied by the up-regulation of ARF/p53/p16(INK4a) and decrease of Ring1b/Bmi1. Our results demonstrated that ARF or p53 deletion cancels the senescence in Mel18-null MEFs, and the fact that p16(INK4a) is up-regulated in double-null MEFs suggests that the ARF/p53 pathway plays a central role in stress-induced senescence. The in vivo binding of Ring1b and E2F3b to the ARF promoter decreased progressively in senescence, and Mel18 inactivation accelerated the exfoliation of Ring1b/E2F3b from the promoter sequence, indicating the cooperation of polycombs/E2F3b on ARF expression and cellular senescence. Taken together, it seems that class II polycomb proteins and E2F3b dually control cellular senescence via the ARF/p53 pathway.

Similar articles

• The differential impact of p16(INK4a) or p19(ARF) deficiency on cell growth and tumorigenesis.

  Sharpless NE, Ramsey MR, Balasubramanian P, Castrillon DH, DePinho RA. Sharpless NE, et al. Oncogene. 2004 Jan 15;23(2):379-85. doi: 10.1038/sj.onc.1207074. Oncogene. 2004. PMID: 14724566

• Transcriptional coactivator Cited2 induces Bmi1 and Mel18 and controls fibroblast proliferation via Ink4a/ARF.

  Kranc KR, Bamforth SD, Bragança J, Norbury C, van Lohuizen M, Bhattacharya S. Kranc KR, et al. Mol Cell Biol. 2003 Nov;23(21):7658-66. doi: 10.1128/MCB.23.21.7658-7666.2003. Mol Cell Biol. 2003. PMID: 14560011 Free PMC article.

• Modulation of the expression of p16INK4a and p14ARF by hnRNP A1 and A2 RNA binding proteins: implications for cellular senescence.

  Zhu D, Xu G, Ghandhi S, Hubbard K. Zhu D, et al. J Cell Physiol. 2002 Oct;193(1):19-25. doi: 10.1002/jcp.10147. J Cell Physiol. 2002. PMID: 12209876

• p53-Dependent and -independent functions of the Arf tumor suppressor.

  Sherr CJ, Bertwistle D, DEN Besten W, Kuo ML, Sugimoto M, Tago K, Williams RT, Zindy F, Roussel MF. Sherr CJ, et al. Cold Spring Harb Symp Quant Biol. 2005;70:129-37. doi: 10.1101/sqb.2005.70.004. Cold Spring Harb Symp Quant Biol. 2005. PMID: 16869746 Review.

• Histone chaperone Jun dimerization protein 2 (JDP2): role in cellular senescence and aging.

  Huang YC, Saito S, Yokoyama KK. Huang YC, et al. Kaohsiung J Med Sci. 2010 Oct;26(10):515-31. doi: 10.1016/S1607-551X(10)70081-4. Kaohsiung J Med Sci. 2010. PMID: 20950777 Review.

Cited by

• Context-dependent actions of Polycomb repressors in cancer.

  Koppens M, van Lohuizen M. Koppens M, et al. Oncogene. 2016 Mar 17;35(11):1341-52. doi: 10.1038/onc.2015.195. Epub 2015 Jun 8. Oncogene. 2016. PMID: 26050622 Review.

• A novel zinc finger protein Zfp277 mediates transcriptional repression of the Ink4a/arf locus through polycomb repressive complex 1.

  Negishi M, Saraya A, Mochizuki S, Helin K, Koseki H, Iwama A. Negishi M, et al. PLoS One. 2010 Aug 24;5(8):e12373. doi: 10.1371/journal.pone.0012373. PLoS One. 2010. PMID: 20808772 Free PMC article.

• Genomic profiling of the transcription factor Zfp148 and its impact on the p53 pathway.

  Zou ZV, Gul N, Lindberg M, Bokhari AA, Eklund EM, Garellick V, Patel AAH, Dzanan JJ, Titmuss BO, Le Gal K, Johansson I, Tivesten Å, Forssell-Aronsson E, Bergö MO, Staffas A, Larsson E, Sayin VI, Lindahl P. Zou ZV, et al. Sci Rep. 2020 Aug 25;10(1):14156. doi: 10.1038/s41598-020-70824-2. Sci Rep. 2020. PMID: 32843651 Free PMC article.

• Emerging roles of E2Fs in cancer: an exit from cell cycle control.

  Chen HZ, Tsai SY, Leone G. Chen HZ, et al. Nat Rev Cancer. 2009 Nov;9(11):785-97. doi: 10.1038/nrc2696. Nat Rev Cancer. 2009. PMID: 19851314 Free PMC article. Review.

• Polycomb group molecule PHC3 regulates polycomb complex composition and prognosis of osteosarcoma.

  Iwata S, Takenobu H, Kageyama H, Koseki H, Ishii T, Nakazawa A, Tatezaki S, Nakagawara A, Kamijo T. Iwata S, et al. Cancer Sci. 2010 Jul;101(7):1646-52. doi: 10.1111/j.1349-7006.2010.01586.x. Epub 2010 Apr 7. Cancer Sci. 2010. PMID: 20491773 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Ovid Technologies, Inc.
  • Wiley

• Molecular Biology Databases

  • Mouse Genome Informatics (MGI)

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal