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:

Distinct pattern of p53 phosphorylation in human tumors

Abstract

The protein product of the tumor suppressor gene p53 is phosphorylated on multiple residues by several protein kinases. Using a battery of 10 antibodies developed against different phosphorylated and acetylated residues of p53, we compared the pattern of p53 phosphorylation and acetylation in tumor-derived cell lines, tumor samples, and non-neoplastic cells. Irrespective of tumor types or the presence of p53 mutation, phosphorylation and acetylation of p53 was substantially higher in samples obtained from tumor tissues than those found in non-transformed samples. Among the 10 sites analysed, phosphorylation of residues 15, 81, 392, and acetylation were among the more frequent modifications. Analysis of two of the more abundant phosphorylation or acetylation sites on p53 is sufficient to detect 72% of tumor-derived p53 proteins. The distinct pattern of p53 phosphorylation and acetylation in human tumors may offer a new means to monitor the status and activity of p53 in the course of tumor development and progression.

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

Access options

Buy this article

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

Figure 1
Figure 2

Similar content being viewed by others

References

  • Banin S, Moyal L, Shieh S, Taya Y, Anderson CW, Chessa L, Smorodinsky N, Prives C, Reiss Y, Shiloh Y, Ziv Y . 1998 Science 281: 1674–1677

  • Bulavin DV, Saito S, Hollander MC, Sakaguchi K, Anderson CW, Appella E, Fornace Jr A.J . 1999 EMBO J. 23: 6845–6854

  • Bullock A, Henckel J, Dedecker B, Johnson C, Nikolova P, Proctor M, Lane D, Fresht A . 1997 Proc. Natl. Acad. Sci. USA 94: 14338–14342

  • Buschmann T, Adler V, Matusevich E, Fuchs SY, Ronai Z . 2000a Cancer Res. 60: 896–900

  • Buschmann T, Minamoto T, Wagle N, Fuchs SY, Adler V, Mai M, Ronai Z . 2000b J. Mol. Biol. 295: 1009–1021

  • Buschmann T, Potapova, O, Bar-Shira A, Ivanov VN, Fuchs SY, Henderson S, Fried VA, Minamoto T, Alarcon-Vargas D, Pincus MR, Gaarde MA, Holbrook NJ, Shiloh Y, Ronai Z . 2001 Mol. Cell. Biol. 21: 2743–2754

  • Canman CE, Lim D-S, Cimprich KA, Taya Y, Tamai K, Sakaguchi K, Appella E, Kastan MB, Siliciano JD . 1998 Science 281: 1677–1679

  • Fernandez PL, Jares P, Rey MJ, Campo E, Cardesa A . 1998 Mol. Pathol. 51: 305–309

  • Foster BA, Coffey HA, Morin MJ, Rastinejad F . 1999 Science 286: 2507–2510

  • Gatti A, Li HH, Traugh JA, Liu X . 2000 Biochemistry 39: 9837–9842

  • Giaccia AJ, Kastan MB . 1998 Genes Dev. 12: 2973–2983

  • Gu W, Roeder RG . 1997 Cell 90: 595–606

  • Gualberto A, Aldape K, Kozakiewicz K, Tlsty T . 1998 Proc. Natl. Acad. Sci. USA 95: 5166–5171

  • Hall P, McKee P, Menage H, Dover R, Lane DP . 1993 Oncogene 8: 203–207

  • Higashimoto Y, Saito S, Tong XH, Hong A, Sakaguchi K, Appella E, Anderson CW . 2000 J. Biol. Chem. 275: 23199–23203

  • Hirao A, Kong YY, Matsuoka S, Wakeham A, Ruland J, Yoshida H, Liu D, Elledge SJ, Mak TW . 2000 Science 287: 1824–1827

  • Hollstein M, Sidranksy D, Vogelstein B, Harris CC . 1991 Science 253: 49–53

  • Huang C, Ma W, Maxiner A, Sun Y, Dong Z . 1999 J. Biol. Chem. 274: 12229–12235

  • Ko LJ, Prives C . 1996 Genes Dev. 10: 1054–1072

  • Lambert PF, Kashanchi F, Radonovich MF, Shiekhattar R, Brady JN . 1998 J. Biol. Chem. 273: 33048–33053

  • Lanyi A, Deb D, Seymour RC, Ludes-Meyers JH, Subler MA, Deb S . 1998 Oncogene 16: 3169–3176

  • Lees-Miller S, Sakaguchi K, Ullrich SJ, Appella E, Anderson CW . 1992 Mol. Cell. Biol. 12: 5041–5049

  • Liu L, Scolnick DM, Trievel RC, Zhang HB, Marmorstein R, Halazonetis TD, Berger Sl . 1999 Mol. Cell Biol. 19: 1202–1209

  • Meek DW . 1998 Cell Signal 10: 159–166

  • Meek DW . 1999 Oncogene 18: 7666–7675

  • Oda K, Arakawa H, Tanaka T, Matsuda K, Tanikawa C, Mori T, Nishimori H, Tamal K, Tokino T, Nakamura Y, Taya Y . 2000 Cell 102: 849–862

  • Price B, Hughes-Davis L, Park S . 1995 Oncogene 11: 73–80

  • Prives C, Hall PA . 1999 J. Pathol. 187: 112–126

  • Reich N, Oren M, Levine AJ . 1983 Mol. Cell. Biol. 3: 2143–2150

  • Sakaguchi K, Herrera J, Saito S, Miki T, Bustin M, Vassilev A, Anderson C, Apella E . 1998 Genes Dev. 12: 2831–2341

  • Sakaguchi K, Saito S, Higashimoto Y, Roy S, Anderson CW, Appella E . 2000 J. Biol. Chem. 275: 9278–9283

  • Satyamoorthy K, Chehab NH, Waterman MJ, Lien MC, El-Deiry WS, Herlyn M, Halazonetis TD . 2000 Cell Growth Differ. 9: 467–474

  • Shieh S, Ikeda M, Taya Y, Prives C . 1997 Cell 91: 325–334

  • Wagner P, Fuchs A, Gotz C, Nastainczyk W, Montenarh M . 1998 Oncogene 8: 105–111

  • Waterman MJF, Stavridi ES, Waterman JL, Halazonetis TD . 1998 Nature Genet. 19: 175–178

Download references

Acknowledgements

We thank Meenhard Herlyn for providing us with melanoma cell lines with normal p53, Michael Comb of NEB for the phospho-p53 antibodies used in this study, and DJ Mazer for editorial assistance. Support from NIH grant CA78419 (to Z Ronai) is gratefully acknowledged.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ze'ev Ronai.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Minamoto, T., Buschmann, T., Habelhah, H. et al. Distinct pattern of p53 phosphorylation in human tumors. Oncogene 20, 3341–3347 (2001). https://doi.org/10.1038/sj.onc.1204458

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204458

Keywords

This article is cited by

Search

Quick links