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 Paper
  • Published:

Role of IFI 16, a member of the interferon-inducible p200-protein family, in prostate epithelial cellular senescence

Oncogene volume 22, pages 4831–4840 (2003)Cite this article

Abstract

Recent studies have implicated interferon signaling in the regulation of cellular senescence. However, the role of specific interferon-inducible proteins in cellular senescence remains to be defined. Here we report that IFI 16, an interferon-inducible transcriptional modulator from the p200-protein family, contributes to cellular senescence of prostate epithelial cells. Normal human prostate epithelial cells (PrEC) in culture expressed detectable levels of IFI 16, and the levels increased more than fourfold when cells approached cellular senescence. Consistent with a role of IFI 16 in cellular senescence, human prostate cancer cell lines either did not express IFI 16 or expressed a variant form, which was primarily detected in the cytoplasm of prostate cancer cells and not in the nucleus. Moreover, overexpression of functional IFI 16 in human prostate cancer cell lines inhibited colony formation. Additionally, ectopic expression of IFI 16 in clonal prostate cancer cell lines was associated with a senescence-like phenotype, production of senescence-associated β-galactosidase (a biochemical marker for cellular senescence), and reduction of S-phase cells in culture. Importantly, upregulation of p21WAF1 and inhibition of E2F-stimulated transcription accompanied inhibition of cell growth by IFI 16 in prostate cancer cell lines. Collectively, our observations support the idea that increased levels of IFI 16 in PrECs contribute to senescence-associated irreversible cell growth arrest.

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
Figure 8
Figure 9
Figure 10

Similar content being viewed by others

References

  • Borden EC, Lindner D, Dreicer R, Hussein M and Peereboom D . (2000). Semin. Cancer Biol., 10, 125–144.

  • Briggs LJ, Johnstone RW, Elliot RM, Xiao CY, Dawson M, Trapani JA and Jans DA . (2001). Biochem. J., 353, 69–77.

  • Campisi J . (2001). Trends Cell. Biol., 11, S27–S31.

  • Castro P, Giri D, Lamb D and Ittmann M . (2003). Prostate, 55, 30–38.

  • Certa U, Seiler M, Padovan E and Spagnoli GC . (2001). Br. J. Cancer, 85, 107–114.

  • Choi J, Shendrik I, Peacocke M, Peehl D, Buttyan R, Ikeguchi EF, Katz AE and Benson MC . (2000). Urology, 56, 160–166.

  • Choubey D . (2000). J. Biol. Regul. Homeost. Agents, 14, 187–192.

  • Choubey D and Kotzin BL . (2002). Front. Biosci., 7, e252–e262.

  • Choubey D and Lengyel P . (1992). J. Cell. Biol., 116, 1333–1341.

  • Choubey D, Li SJ, Datta B, Gutterman JU and Lengyel P . (1996). EMBO J., 15, 5668–5678.

  • Dawson MJ and Trapani JA . (1995). Biochem. Biophys. Res. Commun., 214, 152–162.

  • Decesse JT, Medjkane S, Datto MB and Cremisi CE . (2001). Oncogene, 20, 962–971.

  • DeGregori J . (2002). Biochim. Biophys. Acta, 1602, 131–150.

  • Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I and Pereira-Smith O . (1995). Proc. Natl. Acad. Sci. USA, 92, 9363–9367.

  • Dimri GP, Nakanishi M, Desprez PY, Smith JR and Campisi J . (1996). Mol. Cell. Biol., 16, 2987–2997.

  • D'Souza S, Xin H, Walter S and Choubey D . (2001). J. Biol. Chem., 276, 298–305.

  • Fairbrother WJ, Gordon NC, Humke EW, O'Rourke KM, Starovasnik MA, Yin JP and Dixit VM . (2001). Protein Sci., 10, 1911–1918.

  • Gariglio M, Azzimonti B, Pagano M, Palestro G, De Andrea M, Valente G, Voglino G, Navino L and Landolfo S . (2002). J. Interferon Cytokine Res., 22, 815–821.

  • Garraway LA, Lin D, Signoretti S, Walteregny D, Dilks J, Bhattacharya N and Loda M . (2003). Prostate, 55, 206–218.

  • Gartel AL, Ye X, Goufman E, Shianov P, Hay N, Najmabadi F and Tyner AL . (2001). Proc. Natl. Acad. Sci. USA, 98, 4510–4515.

  • Gribaudo G, Riera L, De Andrea M and Landolfo S . (1999). FEBS Lett., 456, 31–36.

  • Gutterman JU . (1994). Proc. Natl. Acad. Sci. USA, 91, 1198–1205.

  • Gutterman JU and Choubey D . (1999). Cell Growth Differ., 10, 93–100.

  • Harbour JW and Dean DC . (2000). Genes Dev., 14, 2393–2409.

  • Hayflick L . (1965). Exp. Cell. Res., 37, 614–636.

  • Hensler PJ, Annab LA, Barret JC and Pereira-Smith OM . (1994). Mol. Cell. Biol., 14, 2291–2297.

  • Hertel L, Rolle S, De Andrea M, Azzimonti B, Osello R, Gribaudo G, Gariglio M and Landolfo S . (2000). Oncogene, 19, 3598–3608.

  • Jarrard DF, Sarkar S, Shi Y, Yeager TR, Magrane G, Kinoshita H, Nassif N, Meisner L, Newton MA, Waldman FM and Reznikoff CA . (1999). Cancer Res., 59, 2957–2964.

  • Johnstone RW, Kershaw MH and Trapani JA . (1998). Biochemistry, 37, 11924–11931.

  • Johnstone RW and Trapani JA . (1999). Mol. Cell. Biol., 19, 5833–5838.

  • Johnstone RW, Wei W, Greenway A and Trapani JA . (2000). Oncogene, 19, 6033–6042.

  • Jonasch E and Haluska FG . (2001). Oncologist, 6, 34–55.

  • Karlsson C, Stenman G, Vojta PJ, Bongcam-Rudoloff E, Barret JC, Westermark B and Paulsson Y . (1996). Cancer Res., 56, 241–245.

  • Kingsmore SF, Watson ML, Woward TA and Seldin MF . (1989). EMBO J., 8, 4073–4080.

  • Kulaeva OI, Draghici S, Tang L, Kraniak JM, Land SJ and Tainsky MA . (2003). Oncogene, 25, 4118–4127.

  • Landolfo S, Gariglio M, Gribaudo G and Lembo D . (1998). Biochimie, 80, 721–728.

  • Lengyel P, Choubey D, Li SJ and Datta B . (1995). Semin. Virol., 6, 203–213.

  • Mori JY, Rashid A, Leggett BA, Young J, Simms L, Kuehl PM, Langenberg P, Meltzer SJ and Stine OC . (2001). Cancer Res., 61, 6046–6049.

  • Schlaak JF, Hilkens CM, Costa-Pereira AP, Strobl B, Frischauf AM and Kerr IM . (2002). J. Biol. Chem., 277, 49428–49437.

  • Sen GC and Lengyel P . (1992). J. Biol. Chem., 267, 5017–5020.

  • Shou J, Soriano R, Hayward SW, Cunha GR, Williams PM and Gao WQ . (2002). Proc. Natl. Acad. Sci. USA, 99, 2830–2835.

  • Smith JR and Pereira-Smith OM . (1996). Science, 273, 63–67.

  • Stark GR, Kerr IM, Williams BR, Silverman RH and Schreiber RD . (1998). Annu. Rev. Biochem., 67, 227–264.

  • Staub E, Dahl E and Rosenthal A . (2001). Trends Biochem. Sci., 26, 83–85.

  • Untergasser G, Koch HB, Menssen A and Hermeking H . (2002). Cancer Res., 62, 6255–6262.

  • Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG, Ghosh D, Pienta KJ, Sewalt RG, Otte AP, Rubin MA and Chinnaiyan AM . (2002). Nature, 419, 624–629.

  • Wang H, Chatterjee G, Meyer JJ, Liu CJ, Manjunath NA, Bray-Ward P and Lengyel P . (1999). Genomics, 60, 281–294.

  • Webber MM, Bello D and Quader S . (1997). Prostate, 30, 58–64.

  • Wei W, Clarke CJ, Somers GR, Cresswell KS, Loveland KA, Trapani JA and Johnstone RW . (2003). Histochem. Cell. Biol., 119, 45–54.

  • Weinberg RA . (1995). Cell, 81, 323–330.

  • Xin H, D'Souza S, Fang L, Lengyel P and Choubey D . (2001). Oncogene, 20, 6828–6839.

Download references

Acknowledgements

We thank Dr Qin for technical advice and Dr M Tainsky for sharing observations before publication. We also thank Drs O Pereira-Smith, S Campbell, N Mohideen, and E Wojcik for their suggestions and advise during the course of this work. This work was supported by NIH Grants CA69031 and AG022124 (to DC), and AR47307 (to BJN).

Author information

Authors and Affiliations

  1. Departments of Pathology and Radiation Oncology, Stritch School of Medicine, Loyola University Medical Center, Mail code: 114B, 2160 South First Avenue, Maywood, 60153, IL, USA

    Hong Xin, Jonathan Curry, Brian J Nickoloff & Divaker Choubey

  2. Cancer Immunology Program, The Peter MacCallum Cancer Institute, Trescowthick Research Laboratories, St Andrews Place, East Melbourne, Victoria, 3002, Australia

    Ricky W Johnstone

Authors
  1. Hong Xin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jonathan Curry
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ricky W Johnstone
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Brian J Nickoloff
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Divaker Choubey
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Divaker Choubey.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xin, H., Curry, J., Johnstone, R. et al. Role of IFI 16, a member of the interferon-inducible p200-protein family, in prostate epithelial cellular senescence. Oncogene 22, 4831–4840 (2003). https://doi.org/10.1038/sj.onc.1206754

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206754

Keywords

This article is cited by

Search

Advanced search

Quick links