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:

Phosphorylation of HDM2 by Akt

Oncogene volume 21, pages 1955–1962 (2002)Cite this article

Abstract

The HDM2 protein is a key regulator of the tumour suppressor, p53. Control of HDM2 function is critical for normal cell proliferation and stress responses, and it is becoming evident that multiple modifications of HDM2 can regulate its function within cells. In this study we show that HDM2 associated with the serine-threonine kinase, Akt, in response to growth factor stimulation of human primary cells. This association was concurrent with phosphorylation of Akt (at Ser 473), and resulted in elevated expression of HDM2 and enhanced nuclear localization. However, analysis of HDM2 proteins mutated at the consensus Akt recognition sites at serines 166 and 186 indicated that modification at these residues was not sufficient for the increased expression of the protein, which was blocked by the PI3 kinase inhibitor LY294002. Tryptic peptide and mutational analyses revealed evidence for an Akt phosphorylation site in HDM2 additional to the two consensus sites.

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

  • Ashcroft M, Stephens RM, Hallberg B, Downward J, Kaplan DR . 1999 Oncogene 18: 4586–4597

  • Ashcroft M, Taya Y, Vousden KH . 2000 Mol. Cell. Biol. 20: 3224–3233

  • Buschmann T, Fuchs SY, Lee C-G, Pan Z-Q, Ronai Z . 2000 Cell 101: 753–762

  • Cahilly-Snyder L, Yang-Feng T, Francke U, George DL . 1987 Somat. Cell Mol. Genet. 13: 235–244

  • Chen JD, Marechal V, Levine AJ . 1993 Mol. Cell. Biol. 13: 4107–4114

  • Chen J, Lin J, Levine AJ . 1995 Mol. Med. 1: 142–152

  • Fakharzadeh SS, Trusko SP, George DL . 1991 EMBO J. 10: 1565–1569

  • Fang S, Jensen JP, Ludwig RL, Vousden KH, Weissman AM . 2000 J. Biol. Chem 275: 8945–8951

  • Finlay CA . 1993 Mol. Cell. Biol. 13: 301–306

  • Franke TF, Kaplan DR, Cantley LC, Toker A . 1997 Science 275: 628–630

  • Freedman DA, Wu L, Levine AJ . 1999 Cell Mol. Life Sci. 55: 96–107

  • Gotz C, Kartarius S, Scholtes P, Nastainczyk W, Montenarh M . 1999 Eur. J. Biochem. 266: 493–501

  • Guerra B, Gotz C, Wagner P, Montenarh M, Issinger OG . 1997 Oncogene 14: 2683–2688

  • Hay TJ, Meek DW . 2000 FEBS Lett. 478: 183–186

  • Honda R, Yasuda H . 2000 Oncogene 19: 1473–1476

  • Kane LP, Shapiro VS, Stokoe D, Weiss A . 1999 Curr. Biol. 9: 601–604

  • Khosravi R, Maya R, Gottlieb T, Oren M, Shiloh Y, Shkedy D . 1999 Proc. Natl. Acad. Sci. USA 96: 14973–14977

  • Kubbutat MHG, Vousden KH . 1998 Mol. Med. Today 4: 250–256

  • Leri A, Liu Y, Claudio PP, Kajstura J, Wang X, Wang S, Kang P, Malhotra A, Anversa P . 1999 Am. J. Pathol. 154: 567–580

  • Leveillard T, Wasylyk B . 1997 J. Biol. Chem. 272: 30651–30661

  • Lohrum MAE, Ashcroft M, Kubbutat MHG, Vousden KH . 2000 Nature Cell Biol. 2: 179–181

  • Maya R, Balass M, Kim ST, Shkedy D, Leal JF, Shifman O, Moas M, Buschmann T, Ronai Z, Shiloh Y, Kastan MB, Katzir E, Oren M . 2001 Genes Dev. 15: 1067–1077

  • Mayo LD, Turchi JJ, Berberich SJ . 1997 Cancer Res. 57: 5013–5016

  • Mayo LD, Donner DB . 2001 Proc. Natl. Acad. Sci. USA 98: 11598–11603

  • Morrison DK, Heidecker G, Rapp UR, Copeland TD . 1993 J. Biol. Chem. 268: 17309–17316

  • Oliner JD, Kinzler KW, Meltzer PS, George DL, Vogelstein B . 1992 Nature 358: 80–83

  • Olson DC, Marechal V, Momand J, Chen J, Romocki C, Levine AJ . 1993 Oncogene 8: 2353–2360

  • Picksley SM, Vojtesek B, Sparks A, Lane DP . 1994 Oncogene 9: 2523–2529

  • Ries S, Biederer C, Woods D, Shifman O, Shirasawa S, Sasazuki T, McMahon M, Oren M, McCormick F . 2000 Cell 103: 321–330

  • Roth J, Dobbelstein M, Freedman DA, Shenk T, Levine AJ . 1998 EMBO J. 17: 554–564

  • Shaulian E, Resnitzky D, Shifman O, Blandino G, Amsterdam A, Yayon A, Oren M . 1997 Oncogene 15: 2717–2725

  • Stott F, Bates SA, James M, McConnell BB, Starborg M, Brookes S, Palmero I, Hara E, Ryan KM, Vousden KH, Peters G . 1998 EMBO J. 17: 5001–5014

  • Thut CJ, Goodrich JA, Tjian R . 1997 Genes Dev. 11: 1974–1986

  • Weber JD, Kuo M-L, Bothner B, DiGiammarino EL, Kriwacki RW, Roussel MF, Sherr CJ . 2000 Mol. Cell. Biol. 20: 2517–2528

  • Woods DB, Vousden KH . 2001 Exp. Cell Res. 264: 56–66

  • Zhang T, Prives C . 2001 J. Biol. Chem. 276: 29702–29710

  • Zhou BP, Liao Y, Xia W, Zou Y, Spohn B, Hung M-C . 2001 Nature Cell Biol. 3: 973–982

Download references

Acknowledgements

We would like to thank David Stokoe (UCSF) for providing an expression construct containing full-length Akt. We are also grateful to Debbie Morrison and Jurgen Muller (NCI), for helpful discussions and assistance with 2D phosphoamino-acid analysis.

Author information

Authors and Affiliations

  1. CRC, Centre for Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK

    Margaret Ashcroft & Elizabeth J MacRae

  2. Regulation of Cell Growth Laboratory, NCI-FCRDC, Frederick, Maryland, 21702-1201, MD, USA

    Robert L Ludwig, Douglas B Woods, Terry D Copeland, H Oliver Weber & Karen H Vousden

Authors
  1. Margaret Ashcroft
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert L Ludwig
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Douglas B Woods
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Terry D Copeland
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H Oliver Weber
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Elizabeth J MacRae
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Karen H Vousden
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Karen H Vousden.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ashcroft, M., Ludwig, R., Woods, D. et al. Phosphorylation of HDM2 by Akt. Oncogene 21, 1955–1962 (2002). https://doi.org/10.1038/sj.onc.1205276

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205276

Keywords

This article is cited by

Search

Advanced search

Quick links