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:

Binding of RNA to p53 regulates its oligomerization and DNA-binding activity

Abstract

The C-terminus of p53 is responsible for maintaining the latent, non-DNA-binding form of p53. However, the mechanism by which the C-terminus regulates DNA binding is not yet fully understood. We show here that p53 interacts with RNA via its C-terminal domain and that disruption of this interaction, by RNase A treatment, truncation or phosphorylation of the C-terminus, restores DNA-binding activity. Furthermore, the oligomerization of p53 is significantly enhanced by disrupting the interaction between p53 and RNA. These findings suggest that binding of RNA to p53 is involved in the mechanism of p53 latency.

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
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  • Ahn J and Prives C . (2001). Nat. Struct. Biol., 8, 730–732.

  • Bakalkin G, Yakovleva T, Selivanova G, Magnusson KP, Szekely L, Kiseleva E, Klein G, Terenius L and Wiman KG . (1994). Proc. Natl. Acad. Sci. USA, 91, 413–417.

  • Clore GM, Ernst J, Clubb R, Omichinski JG, Kennedy WM, Sakaguchi K, Appella E and Gronenborn AM . (1995). Nat. Struct. Biol., 2, 321–331.

  • Clore GM, Omichinski JG, Sakaguchi K, Zambrano N, Sakamoto H, Appella E and Gronenborn AM . (1994). Science, 265, 386–391.

  • Crook T, Marston NJ, Sara EA and Vousden KH . (1994). Cell, 79, 817–827.

  • Du W and Maniatis T . (1994). Proc. Natl. Acad. Sci. USA, 91, 11318–11322.

  • El-Deiry WS, Kern SE, Pietenpol JA, Kinzler KW and Vogelstein B . (1992). Nat. Genet., 1, 45–49.

  • Espinosa JM and Emerson BM . (2001). Mol. Cell, 8, 57–69.

  • Filhol O, Baudier J, Delphin C, Mackenbach PL, Chambaz EM and Cochet C . (1992). J. Biol. Chem., 267, 20577–20583.

  • Fiscella M, Zambrano N, Ullrich SJ, Unger T, Lin D, Cho B, Mercer WE, Anderson CW and Appella E . (1994). Oncogene, 9, 3249–3257.

  • Fontoura BM, Atienza CA, Sorokina EA, Morimoto T and Carroll RB . (1997). Mol. Cell Biol., 17, 3146–3154.

  • Fontoura BM, Sorokina EA, David E and Carroll RB . (1992). Mol. Cell Biol., 12, 5145–5151.

  • Fuchs B, O'Connor D, Fallis L, Scheidtmann KH and Lu X . (1995). Oncogene, 10, 789–793.

  • Funk WD, Pak DT, Karas RH, Wright WE and Shay JW . (1992). Mol. Cell Biol., 12, 2866–2871.

  • Guo A, Salomoni P, Lou J, Shih A, Zhong S, Gu W and Pandolfi PP . (2000). Nat. Cell Biol., 2, 730–736.

  • Halazonetis TD, Davis LJ and Kandil AN . (1993). EMBO J., 12, 1021–1028.

  • Hao M, Lowy AM, Kaopoor M, Deffie A, Liu G and Lozano G . (1996). J. Biol. Chem., 271, 29380–29385.

  • Hupp TR and Lane DP . (1995). J. Biol. Chem., 270, 18165–18174.

  • Hupp TR, Meek DW, Midgley CA and Lane DP . (1992). Cell, 71, 875–886.

  • Hupp TR, Meek DW, Midgley CA and Lane DP . (1993). Nucleic Acids Res., 21, 3167–3174.

  • Imamura T, Izumi H, Nagatani G, Ise T, Nomoto M, Iwamoto Y and Kohno K . (2001). J. Biol. Chem., 276, 7534–7540.

  • Izumi H, Ohta R, Nagatani G, Ise T, Nakayama Y, Nomoto M and Kohn K . (2003). Biochem. J., 373, 713–722.

  • Jayaraman J and Prives C . (1995). Cell, 81, 1021–1029.

  • Kaeser MD and Iggo RD . (2002). Proc. Natl. Acad. Sci. USA, 99, 95–100.

  • Keller DM, Zeng X, Wang Y, Zhang QH, Kapoor M, Shu H, Goodman R, Lozano G, Zhao Y and Lu H . (2001). Mol. Cell, 7, 283–292.

  • Kulesz-Martin MF, Lisafeld B, Huang H, Kisiel ND and Lee L . (1994). Mol. Cell Biol., 14, 1698–1708.

  • Lee S, Elenbaas B, Levine A and Griffith J . (1995). Cell, 81, 1013–1020.

  • Lee W, Harvey TS, Yin Y, Yau P, Litchfield D and Arrowsmith CH . (1994). Nat. Struct. Biol., 1, 877–890.

  • Levine AJ . (1997). Cell, 88, 323–331.

  • Marechal V, Elenbaas B, Piette J, Nicolas JC and Levine AJ . (1994). Mol. Cell Biol., 14, 7414–7420.

  • Marston NJ, Ludwig RL and Vousden KH . (1998). Oncogene, 16, 3123–3131.

  • Meek DW, Simon S, Kikkawa U and Eckhart W . (1990). EMBO J., 9, 3253–3260.

  • Miller SJ, Suthiphongchai T, Zambetti GP and Ewen ME . (2000). Mol. Cell Biol., 20, 8420–8431.

  • Minamoto T, Buschmann T, Habelhah H, Matusevich E, Tahara H, Boerresen-Dale AL, Harris C, Sidransky D and Ronai Z . (2001). Oncogene, 20, 3341–3347.

  • Mosner J, Mummenbrauer T, Bauer C, Sczakiel G, Grosse F and Deppert W . (1995). EMBO J., 14, 4442–4449.

  • Okamoto T, Izumi H, Imamura T, Takano H, Ise T, Uchiumi T, Kuwano M and Kohno K . (2000). Oncogene, 19, 6194–6202.

  • Sakaguchi K, Sakamoto H, Lewis MS, Anderson CW, Erickson JW, Appella E and Xie D . (1997). Biochemistry, 36, 10117–10124.

  • Samad A and Carroll RB . (1991). Mol. Cell Biol., 11, 1598–1606.

  • Torigoe T, Izumi H, Yoshida Y, Ishiguchi H, Okamoto T, Itoh H and Kohno K . (2003). Nucleic Acids Res., 31, 4523–4530.

  • Wang Y, Reed M, Wang P, Stenger JE, Mayr G, Anderson ME, Schwedes JF and Tegtmeyer P . (1993). Genes Dev., 7, 2575–2586.

  • Yakovleva T, Pramanik A, Terenius L, Ekstrom TJ and Bakalkin G . (2002). Trends Biochem. Sci., 27, 612–618.

  • Yoshida Y, Izumi H, Ise T, Uramoto H, Torigoe T, Ishiguchi H, Murakami T, Tanabe M, Nakayama Y, Itoh H, Kasai H and Kohno K . (2002). Biochem. Biophys. Res. Commun., 295, 945–951.

  • Yoshida Y, Izumi H, Torigoe T, Ishiguchi H, Itoh H, Kang D and Kohno K . (2003). Cancer Res., 63, 3729–3734.

Download references

Acknowledgements

This work was supported by MEXT. KAKENHI (13218132).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kimitoshi Kohno.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yoshida, Y., Izumi, H., Torigoe, T. et al. Binding of RNA to p53 regulates its oligomerization and DNA-binding activity. Oncogene 23, 4371–4379 (2004). https://doi.org/10.1038/sj.onc.1207583

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1207583

Keywords

This article is cited by

Search

Quick links