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 Article
  • Published:

AP2α alters the transcriptional activity and stability of p53

Oncogene volume 25, pages 2148–2159 (2006)Cite this article

Abstract

AP2α and p53 form nuclear complexes that establish a functional partnership, which regulates the expression of certain genes involved in cell growth and metastasis. The growth effects of AP2α are mediated through p21WAF1/CIP1 and the ability for AP2α to coactivate p21 requires p53. Herein, we have localized the AP2-binding region of p53 to amino acids 305–375. Analysis of 26 distinct p53 alleles established a correlation between AP2α binding and transcriptional coactivation. The L350P point mutation was the only nonbinding allele that retained normal transcriptional activity by reporter assay. Although both wild-type and L350P alleles facilitated binding of AP2α to the p21 promoter, the L350P allele was significantly reduced in its ability to induce the endogenous p21 gene, demonstrating a striking difference in activity comparing reporter assays with activation of endogenous p53 target genes. Interestingly, expression of AP2 in the absence of radiation repressed p53-mediated induction of p21 and this effect was explained by a reduction in p53 stability induced by AP2α overexpression. We conclude that AP2α has competing effects on p53 activity through coactivation and decreased stability. These findings may provide a mechanism to account for the discrepancies reported for the association between AP2 and p21 expression in tumor tissue.

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

Similar content being viewed by others

References

  • Anttila MA, Kellokoski JK, Moisio KI, Mitchell PJ, Saarikoski S, Syrjanen K et al. (2000). Br J Cancer 82: 1974–1983.

  • Astrom A, Pettersson U, Voorhees JJ . (1992). J Biol Chem 267: 25251–25255.

  • Auman HJ, Nottoli T, Lakiza O, Winger Q, Donaldson S, Williams T . (2002). Development 129: 2733–2747.

  • Baldi A, Santini D, Battista T, Dragonetti E, Ferranti G, Petitti T et al. (2001). J Cell Biochem 83: 364–372.

  • Bar-Eli M . (1999). Cancer Metast Rev 18: 377–385.

  • Bar-Eli M . (2001). Pigment Cell Res 14: 78–85.

  • Batsche E, Muchardt C, Behrens J, Hurst HC, Cremisi C . (1998). Mol Cell Biol 18: 3647–3658.

  • Bosher JM, Totty NF, Hsuan JJ, Williams T, Hurst HC . (1996). Oncogene 13: 1701–1707.

  • Bosher JM, Williams T, Hurst HC . (1995). Proc Natl Acad Sci USA 92: 744–747.

  • Brokx RD, Bolewska-Pedyczak E, Gariepy J . (2003). J Biol Chem 278: 2327–2332 Epub 2002 Nov 13.

  • Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown JP et al. (1998). Science 282: 1497–1501.

  • Buschmann T, Lin Y, Aithmitti N, Fuchs SY, Lu H, Resnick-Silverman L et al. (2001). J Biol Chem 276: 13852–13857 Epub 2001 Feb 1.

  • Chene P . (2001). Oncogene 20: 2611–2617.

  • deConinck EC, McPherson LA, Weigel RJ . (1995). Mol Cell Biol 15: 2191–2196.

  • Doerksen LF, Bhattacharya A, Kannan P, Pratt D, Tainsky MA . (1996). Nucleic Acids Res 24: 2849–2856.

  • Feng W, Williams T . (2003). Mol Cell Neurosci 24: 460–475.

  • Gee JM, Robertson JF, Ellis IO, Nicholson RI, Hurst HC . (1999). J Pathol 189: 514–520.

  • Gershenwald JE, Sumner W, Calderone T, Wang Z, Huang S, Bar-Eli M . (2001). Oncogene 20: 3363–3375.

  • Haupt Y, Maya R, Kazaz A, Oren M . (1997). Nature 387: 296–299.

  • Hilger-Eversheim K, Moser M, Schorle H, Buettner R . (2000). Gene 260: 1–12.

  • Jiang JG, DeFrances MC, Machen J, Johnson C, Zarnegar R . (2000). Biochem Biophys Res Commun 272: 882–886.

  • Karjalainen JM, Kellokoski JK, Eskelinen MJ, Alhava EM, Kosma VM . (1998). J Clin Oncol 16: 3584–3591.

  • Katsel PL, Greenstein RJ . (2001). J Biol Chem 276: 752–758.

  • Kern SE, Pietenpol JA, Thiagalingam S, Seymour A, Kinzler KW, Vogelstein B . (1992). Science 256: 827–830.

  • Kim HS, Hong SJ, LeDoux MS, Kim KS . (2001). J Neurochem 76: 280–294.

  • Kubbutat MH, Jones SN, Vousden KH . (1997). Nature 387: 299–303.

  • Leung KM, Po LS, Tsang FC, Siu WY, Lau A, Ho HT et al. (2002). Cancer Res 62: 4890–4893.

  • Lipponen P, Aaltomaa S, Kellokoski J, Ala-Opas M, Kosma V . (2000). Eur Urol 37: 573–578.

  • Marreiros A, Dudgeon K, Dao V, Grimm MO, Czolij R, Crossley M et al. (2005). Oncogene 24: 637–649.

  • McPherson LA, Baichwal VR, Weigel RJ . (1997). Proc Natl Acad Sci USA 94: 4342–4347.

  • McPherson LA, Loktev AV, Weigel RJ . (2002). J Biol Chem 277: 45028–45033.

  • McPherson LA, Weigel RJ . (1999). Nucleic Acids Res 27: 4040–4049.

  • Mertens PR, Steinmann K, Alfonso-Jaume MA, En-Nia A, Sun Y, Lovett DH . (2002). J Biol Chem 277: 24875–24882.

  • Modugno M, Tagliabue E, Ardini E, Berno V, Galmozzi E, De Bortoli M et al. (2002). Oncogene 21: 7478–7487.

  • Moser M, Imhof A, Pscherer A, Bauer R, Amselgruber W, Sinowatz F et al. (1995). Development 121: 2779–2788.

  • Moser M, Pscherer A, Roth C, Becker J, Mucher G, Zerres K et al. (1997). Genes Dev 11: 1938–1948.

  • Nottoli T, Hagopian-Donaldson S, Zhang J, Perkins A, Williams T . (1998). Proc Natl Acad Sci USA 95: 13714–13719.

  • Oulad-Abdelghani M, Bouillet P, Chazaud C, Dolle P, Chambon P . (1996). Exp Cell Res 225: 338–347.

  • Pellikainen MJ, Pekola TT, Ropponen KM, Kataja VV, Kellokoski JK, Eskelinen MJ et al. (2003). J Clin Pathol 56: 214–220.

  • Ren Y, Liao WS . (2001). J Biol Chem 13: 13.

  • Ropponen KM, Kellokoski JK, Lipponen PK, Pietilainen T, Eskelinen MJ, Alhava EM et al. (1999). Br J Cancer 81: 133–140.

  • Ropponen KM, Kellokoski JK, Pirinen RT, Moisio KI, Eskelinen MJ, Alhava EM et al. (2001). J Clin Pathol 54: 533–538.

  • Terui T, Murakami K, Takimoto R, Takahashi M, Takada K, Murakami T et al. (2003). Cancer Res 63: 8948–8954.

  • Vega FM, Sevilla A, Lazo PA . (2004). Mol Cell Biol 24: 10366–10380.

  • Wajapeyee N, Somasundaram K . (2003). J Biol Chem 278: 52093–52101.

  • Wang YH, Tsay YG, Tan BC, Lo WY, Lee SC . (2003). J Biol Chem 278: 25568–25576 Epub 2003 Apr 30.

  • West-Mays JA, Zhang J, Nottoli T, Hagopian-Donaldson S, Libby D, Strissel KJ et al. (1999). Dev Biol 206: 46–62.

  • Williams T, Admon A, Luscher B, Tjian R . (1988). Genes Dev 2: 1557–1569.

  • Wulf GM, Liou YC, Ryo A, Lee SW, Lu KP . (2002). J Biol Chem 277: 47976–47979 Epub 2002 Oct 17.

  • Xu Y . (2003). Cell Death Differ 10: 400–403.

  • Zeng YX, Somasundaram K, el-Deiry WS . (1997). Nat Genet 15: 78–82.

  • Zhang J, Brewer S, Huang J, Williams T . (2003). Dev Biol 256: 127–145.

  • Zhang J, Hagopian-Donaldson S, Serbedzija G, Elsemore J, Plehn-Dujowich D, McMahon AP et al. (1996). Nature 381: 238–241.

  • Zhao F, Satoda M, Licht JD, Hayashizaki Y, Gelb BD . (2001). J Biol Chem 276: 40755–40760.

Download references

Acknowledgements

This work was supported, in part, by NIH Grant R01 CA77350 and by a generous gift from the Kristen Olewine Milke Breast Cancer Research Fund. We thank Dr Dan Rosson for assistance with GFP sorting using flow cytometry and the KCC Nucleic Acid Facility for assistance with utilizing the ABI 7000 for Q PCR.

Author information

Author notes

  1. P R Stabach and M M Thiyagarajan: These two authors contributed equally to this work.

Authors and Affiliations

  1. Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA

    P R Stabach, M M Thiyagarajan, G W Woodfield & R J Weigel

  2. Department of Surgery, University of Iowa, Iowa City, IA, USA

    G W Woodfield & R J Weigel

Authors
  1. P R Stabach
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M M Thiyagarajan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G W Woodfield
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R J Weigel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R J Weigel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stabach, P., Thiyagarajan, M., Woodfield, G. et al. AP2α alters the transcriptional activity and stability of p53. Oncogene 25, 2148–2159 (2006). https://doi.org/10.1038/sj.onc.1209250

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1209250

Keywords

This article is cited by

Search

Advanced search

Quick links