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:

A novel PHD-finger motif protein, p47ING3, modulates p53-mediated transcription, cell cycle control, and apoptosis

Abstract

A candidate tumor suppressor gene, p33ING1, was previously identified by using the genetic suppressor element methodology. p33ING1 cooperates with p53 and plays a significant role in p53-mediated cellular processes. Recently, we have identified p33ING2, which shows a sequence homology similar to p33ING1 and modulates p53 function. In the present study, we identified and characterized another ‘ING family’ gene. The estimated molecular weight of the encoded protein is 46.8 kDa, thus, we named it p47ING3. The p47ING3 gene is located at chromosome 7q31.3 and consists of 12 exons that encode 418 amino acids. A computational domain search revealed a C-terminal PHD-finger motif. Such motifs are common in proteins involved in chromatin remodeling. p47ING3 is highly expressed in some normal human tissues or organs, including the spleen, testis, skelet al muscle, and heart. p47ING3 expression levels varied among cancer cell lines. p47ING3 overexpression resulted in a decreased population of cells in S phase, a diminished colony-forming efficiency, and induced apoptosis in RKO cells, but not in RKO-E6 cells with inactivated p53. p47ING3 activates p53-transactivated promoters, including promoters of p21/waf1 and bax. Thus, we have isolated a novel ING family gene, p47ING3, which modulates p53-mediated transcription, cell cycle control, and apoptosis.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

  • Barlev NA, Liu L, Chehab NH, Mansfield K, Harris KG, Halazonetis TD and Berger SL . (2001). Mol. Cell, 8, 1243–1254.

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

  • Garkavtsev I, Grigorian IA, Ossovskaya VS, Chernov MV, Chumakov PM and Gudkov AV . (1998). Nature, 391, 295–298.

  • Garkavtsev I, Kazarov A, Gudkov A and Riabowol K . (1996). Nat. Genet., 14, 415–420.

  • Garkavtsev I, Kazarov A, Gudkov A and Riabowol K . (1999). Nat. Genet., 23, 373.

  • Garkavtsev I and Riabowol K . (1997). Mol. Cell. Biol., 17, 2014–2019.

  • Greenblatt MS, Bennett WP, Hollstein M and Harris CC . (1994). Cancer Res., 54, 4855–4878.

  • Gu W and Roeder RG . (1997). Cell, 90, 595–606.

  • Helbing CC, Veillette C, Riabowol K, Johnston RN and Garkavtsev I . (1997). Cancer Res., 57, 1255–1258.

  • Hollstein M, Hergenhahn M, Yang Q, Bartsch H, Wang ZQ and Hainaut P . (1999). Mutat. Res., 431, 199–209.

  • Hollstein M, Sidransky D, Vogelstein B and Harris CC . (1991). Science, 253, 49–53.

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

  • Kessis TD, Slebos RJ, Nelson WG, Kastan MB, Plunkett BS, Han SM, Lorincz AT, Hedrick L and Cho KR . (1993). Proc. Natl. Acad. Sci. USA, 90, 3988–3992.

  • Kuzmichev A, Zhang Y, Erdjument Bromage H, Tempst P and Reinberg D . (2002). Mol. Cell. Biol., 22, 835–848.

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

  • Loewith R, Meijer M, Lees-Miller SP, Riabowol K and Young D . (2000). Mol. Cell. Biol., 20, 3807–3816.

  • Loewith R, Smith JS, Mejer M, Williams TJ, Bachman N, Boeke JD and Young D . (2001). J. Biol. Chem., 276, 24068–24074.

  • Luo J, Nikolaev AY, Imai S, Chen D, Su F, Shiloh A, Guarente L and Gu W . (2001). Cell, 107, 137–148.

  • Miyashita T and Reed JC . (1995). Cell, 80, 293–299.

  • Nagashima M, Shiseki M, Miura K, Hagiwara K, Linke SP, Pedeux R, Wang XW, Yokota J, Riabowol K and Harris CC . (2001). Proc. Natl. Acad. Sci. USA, 98, 9671–9676.

  • Nourani A, Doyon Y, Utley RT, Allard S, Lane WS and Cote J . (2001). Mol. Cell. Biol., 22, 7629–7640.

  • Prives C and Manley JL . (2001). Cell, 107, 815–818.

  • Saito A, Furukawa T, Fukushige S, Koyama S, Hoshi M, Hayashi Y and Horii A . (2000). J. Hum. Genet., 45, 177–181.

  • Sakaguchi K, Herrera JE, Saito S, Miki T, Bustin M, Vassilev A, Anderson CW and Appela E . (1998). Genes Dev., 12, 2831–2841.

  • Skowyra D, Zeremski M, Neznanov N, Li M, Choi Y, Uesugi M, Hauser CA, Gu W, Gudkov AV and Qin J . (2001). J. Biol. Chem., 276, 8734–8739.

  • Vogelstein B, Lane D and Levine AJ . (2000). Nature, 408, 307–310.

Download references

Acknowledgements

We thank Drs B Vogelstein and W El-Deiry for providing the WWW-Luc-p21 and PGL3-Luc-Bax vectors, Dr E Appella for providing a specific antibody for phosphorylated p53 at Ser-46 and advice on preparing the anti-p47ING3 antibody, and Ms D Dudek for editorial and graphic assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Curtis C Harris.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nagashima, M., Shiseki, M., Pedeux, R. et al. A novel PHD-finger motif protein, p47ING3, modulates p53-mediated transcription, cell cycle control, and apoptosis. Oncogene 22, 343–350 (2003). https://doi.org/10.1038/sj.onc.1206115

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206115

Keywords

This article is cited by

Search

Quick links