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.

  • Short Report
  • Published:

Retinoblastoma susceptibility gene product pRB activates hypoxia-inducible factor-1 (HIF-1)

Oncogene volume 24, pages 1802–1808 (2005)Cite this article

Abstract

Hypoxia-inducible factor-1 alpha (HIF-1α) constitutes a regulatory subunit of HIF-1, a major transcriptional activator of genes that coordinate physiological and pathological responses towards hypoxia. In order to identify novel interaction partners of HIF-1α we have applied T7 phage display system and identified a domain inherent in the retinoblastoma protein (pRB). The interaction between pRB and HIF-1α was confirmed by in vitro experiments and in transfected cells. Thereby, an HIF-1α domain spanning amino acids 530–694 was mapped to be required for pRB binding. Overexpression of pRB provoked transcriptional activation of HIF-1α under normoxia. Furthermore, the domain of pRB identified to bind HIF-1α in vitro is sufficient to cause HIF-1α transcriptional activation with the further notion that phosphorylation deficient pRB shows stronger HIF-1α transactivation. Using ChIP analysis, we show that HIF-1α responsive elements (HREs) are precipitated using α-pRB antibodies. Additionally, a functional interaction between pRB and HIF-1α is confirmed by showing that HIF-1α reverses the transcription repressor function of pRB.

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

Similar content being viewed by others

References

  • Amellem O, Stokke T, Sandvik JA and Pettersen EO . (1996). Exp. Cell Res., 227, 8106–8115.

  • An WG, Kanekal M, Simon MC, Maltepe E, Blagosklonny MV and Neckers LM . (1998). Nature, 392, 405–408.

  • Arany Z, Huang LE, Eckner R, Bhattacharya S, Jiang C, Goldberg MA, Bunn HF and Livingston DM . (1996). Proc. Natl. Acad. Sci. USA, 93, 12969–12973.

  • Bae M-K, Ahn M-Y, Jeong J-W, Bae M-H, Lee YM, Bae S-K, Park J-W, Kim K-R and Kim K-W . (2002). J. Biol. Chem., 277, 9–12.

  • Bookstein R and Lee W-H . (1991). Crit. Rev. Oncogene, 2, 211–227.

  • Bunn HF and Poyton RO . (1996). Physiol. Rev., 76, 839–885.

  • Carrero P, Okamoto K, Coumailleau P, O’Brien S, Tanaka H and Poellinger L. . (2000). Mol. Cell. Biol., 20, 402–415.

  • Chen P-L, Riley DJ, Chen Y and Lee W-H . (1996a). Genes Dev., 10, 2794–2804.

  • Chen P-L, Riley DJ, Chen-Kiang S and Lee W-H . (1996b). Proc. Natl. Acad. Sci. USA, 93, 465–469.

  • Cho S, Choi Y-J, Kim J-M, Jeong S-T, Kim J-H, Kim S-H and Ryu S-E . (2001). FEBS Lett., 498, 62–66.

  • Chun Y-S, Kim M-S and Park J-W . (2002). Korean Med. Sci., 17, 581–588.

  • Cockman M, Masson N, Mole D, Jaakola P, Chang G, Clifford S, Maher E, Pugh C, Ratcliffe P and Maxwell P. . (2000). J. Biol. Chem., 275, 25733–25741.

  • Danielsen T, Hvidsen M, Stokke T, Solberg K and Rofstad EK . (1998). Br. J. Cancer, 78, 1547–1558.

  • Gradin K, McGuire J, Wenger RH, Kvietikova I, Whitelaw ML, Toftgard R, Tora L, Gassmann M and Poellinger L . (1996). Mol. Cell. Biol., 16, 5221–5231.

  • Green SL, Freiberg RA and Giaccia AJ . (2001). Mol. Cell. Biol., 21, 1196–1206.

  • Gu W, Schneider JW, Condorelli G, Kaushal S, Mahdavi V and Nadal-Ginard B . (1993). Cell, 72, 309–324.

  • Huang LE and Bunn HF . (2003). J. Biol. Chem., 278, 19575–19578.

  • Hui A-M, Li X, Makuuchi M, Takayama T and Kubota K . (1999). Int. J. Cancer (Pred. Oncol.), 84, 604–608.

  • Kaelin WG . (1999). Bioessays, 21, 950–958.

  • Kondo K and Kaelin Jr WG . (2001). Exp. Cell. Res., 264, 117–125.

  • Krtolica A and Ludlow JW . (1996). Cancer Res., 56, 1168–1173.

  • Ludlow JW, Howell RL and Smith HC . (1993). Oncogene, 8, 331–339.

  • Mahon PC, Hirota K and Semenza GL . (2001). Genes Dev., 15, 2675–2686.

  • Marlowe JL, Knudsen ES, Schwemberger S and Puga A . (2004). J. Biol. Chem., 279, 29013–29022.

  • Nead MA, Baglia LA, Antinore MJ, Ludlow JW and McCance DJ . (1998). EMBO J., 17, 2342–2352.

  • Nevins JR . (2001). Hum. Mol. Genet., 10, 699–703.

  • O’Conner DJ and Lu X . (2000). Oncogene, 19, 2369–2376.

  • Puga A, Barnes SJ, Dalton TP, Chang C, Knudsen ES and Maier MA . (2000). J. Biol. Chem., 275, 1943–2950.

  • Rodi DJ and Makowski L . (1999). Curr. Opin. Biotechnol., 10, 87–93.

  • Sandau KB, Zhou J, Kietzmann T and Brüne B . (2001). J. Biol. Chem., 276, 39805–39811.

  • Sang N, Fang J, Srinivas V, Leshchinsky I and Caro J . (2002). Mol. Cell. Biol., 22, 2984–2992.

  • Sche PP, McKenzie KM, White JD and Austin DJ . (1999). Chem. Biol., 6, 707–716.

  • Semenza GL . (2000). Genes Dev., 14, 1983–1991.

  • Semenza GL . (2001). Curr. Opin. Cell Biol., 13, 167–171.

  • Spencer VA, Sun J-M, Li L and Davie JR . (2003). Methods, 31, 67–75.

  • Wang F, Zhang R, Beischlag TV, Muchardt C, Yaniv M and Hankinson O . (2004). J. Biol. Chem., 279, 46733–46741.

  • Wenger RH . (2002). FASEB J., 16, 1151–1162.

  • Zheng L and Lee WH . (2001). Exp. Cell Res., 264, 2–18.

Download references

Acknowledgements

We thank S Mittnacht, P Ratcliffe, C Adrain, S Cho, T Kietzmann, A Puga and S Frisch for plasmids. The work was supported by grants from the Sander Foundation (2002.088.1), Deutsche Forschungsgemeinschaft (Br 999) and German Cancer League (10-2008-Br2).

Author information

Authors and Affiliations

  1. Department of Medicine IV-Experimental Division, Faculty of Medicine, University of Erlangen-Nürnberg, 91054, Erlangen, Germany

    Andreja Budde & Nicole Schneiderhan-Marra

  2. Institute of Zoology, Molecular Evolution and Genomics, University of Heidelberg, 69120, Heidelberg, Germany

    Gabriele Petersen

  3. Department of Cell Biology, Faculty of Biology, University of Kaiserslautern, 67663, Kaiserslautern, Germany

    Andreja Budde, Nicole Schneiderhan-Marra & Bernhard Brüne

Authors
  1. Andreja Budde
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nicole Schneiderhan-Marra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gabriele Petersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bernhard Brüne
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bernhard Brüne.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Budde, A., Schneiderhan-Marra, N., Petersen, G. et al. Retinoblastoma susceptibility gene product pRB activates hypoxia-inducible factor-1 (HIF-1). Oncogene 24, 1802–1808 (2005). https://doi.org/10.1038/sj.onc.1208369

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1208369

Keywords

This article is cited by

Search

Advanced search

Quick links