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:

CBP and histone deacetylase inhibition enhance the transactivation potential of the HOXB7 homeodomain-containing protein

Oncogene volume 18, pages 4007–4014 (1999)Cite this article

Abstract

Homeodomain-containing proteins are transcription factors regulating the coordinated expression of multiple target genes involved in development, differentiation and cellular transformation. In this study, we demonstrated that HOXB7, one member of this family, behaved as a transactivator in breast cancer cells. Deletion of either the HOXB7 N-terminal domain or the C-terminal acidic tail abolished this transcriptional effect, suggesting a combination of distinct functional transactivating domains. HOXB7 physically interacted both in vitro and in vivo with the coactivator CREB-binding protein (CBP). This interaction led to an enhanced transactivating potential and required the N-terminal of HOXB7 as well as two domains located at the C-terminal part of CBP. Moreover, trichostatin A, a deacetylase inhibitor, strongly enhanced the transcriptional properties of HOXB7. Our data therefore indicate that HOX proteins can directly interact with CBP and that acetylation/deacetylation may regulate their transcriptional properties.

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

Similar content being viewed by others

References

  • Arany Z, Newsome D, Oldread E, Livingston DM and Eckner R. . 1995 Nature 374: 81–84.

  • Avantaggiati ML, Ogryzko V, Gardner K, Giordano A, Levine AS and Kelly K. . 1997 Cell 89: 1175–1184.

  • Bannister AJ and Kouzarides T. . 1996 Nature 384: 641–643.

  • Care A, Silvani A, Meccia E, Mattia G, Stoppacciaro A, Parmiani G, Peschle C and Colombo MP. . 1996 Mol. Cell. Biol. 16: 4842–4851.

  • Chakravarti D, LaMorte VJ, Nelson MC, Nakajima T, Schulman IG, Juguilon H, Montminy M and Evans RM. . 1996 Nature 383: 99–103.

  • Chang CP, Shen WF, Rozenfeld S, Lawrence HJ, Largman C and Cleary M. . 1995 Genes Dev. 9: 663–674.

  • Chang CP, De Vito I and Cleary ML. . 1997 Mol. Cell. Biol. 17: 81–88.

  • Chariot A, Senterre-Lesenfants S, Sobel ME and Castronovo V. . 1998 J. Cell. Biochem. 71: 46–54.

  • Chrivia JC, Kwok RP, Lamb N, Hagiwara M, Montminy MR and Goodman R. . 1993 Nature 365: 855–859.

  • Corsetti MT, Briata P, Sanseverino L, Daga A, Airoldi I, Simeone A, Palmisano G, Angelini C, Boncinelli E and Corte G. . 1992 Nucleic Acid Res. 20: 4465–4472.

  • Deguchi Y, Moroney JF and Kehrl J. . 1991 Blood 78: 445–450.

  • Eckner R, Ewen ME, Newsome D, Gerdes M, DeCaprio JA, Lawrence JB and Livingston DM. . 1994 Genes Dev. 8: 869–884.

  • Favier B and Dollé P. . 1997 Mol. Hum. Reprod. 3: 115–131.

  • Feng XH, Zhang Y, Wu RY and Derynck R. . 1998 Genes Dev. 12: 2153–2163.

  • Gehring WJ, Affolter M and Bürglin T. . 1994 Ann. Rev. Biochem. 63: 487–526.

  • Giles RH, Peters DJ and Breuning MH. . 1998 Trends Genet. 14: 178–183.

  • Gu W and Roeder RG. . 1997a Nature 387: 819–823.

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

  • Hanstein B, Eckner R, Direnzo J, Halachmi S, Liu H, Searcy B, Kurokawa R and Brown M. . 1996 Proc. Natl. Acad. Sci. USA 93: 11540–11545.

  • Imhof A, Yang X-J, Ogryzko VV, Nakatani Y, Wolffe AP and Ge H. . 1997 Curr. Biol. 7: 689–692.

  • Janknecht R, Wells NJ and Hunter T. . 1998 Genes Dev. 12: 2114–2119.

  • Kaelin Jr WG, Pallas DC, DeCaprio JA, Kaye FJ and Livingston DM. . 1991 Cell 64: 521–532.

  • Kamei Y, Xu L, Heinzel T, Torchia J, Kurowaka R, Gloss B, Lin SC, Heyman RA, Rose DW, Glass CK and Rosenfeld MG. . 1996 Cell 85: 403–414.

  • Kawasaki H, Eckner R, Yao TP, Taira K, Chiu R, Livingston DM and Yokoyama KK. . 1998 Nature 393: 284–289.

  • Levine M and Hoey T. . 1988 Cell 55: 537–540.

  • Li H and Don Chen J. . 1998 J. Biol. Chem. 273: 5948–5954.

  • Lill MC, Fuller JF, Herzig R, Crooks GM and Gasson JC. . 1995 Blood 85: 692–697.

  • Lill NL, Grossman SR, Ginsberg D, DeCaprio J and Livingston DM. . 1997 Nature 387: 823–826.

  • Magli MC. . 1998 Biotherapy 10: 279–294.

  • Mann RS and Chan SK. . 1996 Trends Genet. 12: 258–262.

  • Mark M, Rijli FM and Chambon P. . 1997 Pediatr. Res. 42: 421–429.

  • Martinez-Balbas MA, Bannister AJ, Martin K, Haus-Seuffert P, Meisterernst M and Kouzarides T. . 1998 EMBO J. 17: 2886–2893.

  • McCaffrey PG, Newsome DA, Fibach E, Yoshida M and Su MS. . 1997 Blood 90: 2075–2083.

  • Minucci S, Horn V, Bhattacharyya N, Russanova V, Ogryzko VV, Gbriele L, Howard BH and Ozato K. . 1997 Proc. Natl. Acad. Sci. USA 94: 11295–11300.

  • Neish AS, Anderson SF, Schlegel BP, Wei W and Parvin JD. . 1998 Nucleic Acids Res. 26: 847–853.

  • Neumann JF, Morency C and Russian K. . 1987 Biotechniques 5: 444–447.

  • Ogryzko VV, Schiltz RL, Russanova V, Howard BH and Nakatani Y. . 1996 Cell 87: 953–959.

  • Perkins ND, Felzien LK, Betts JC, Leung K, Beach DH and Nabel GJ. . 1997 Science 275: 523–527.

  • Petrij F, Giles RH, Dauwerse HG, Saris JJ, Hennekam RCM, Masuno M, Tommerup N, van Ommen GJB, Goodman RH, Peters DJM and Breuning MH. . 1995 Nature 376: 348–351.

  • Sanlioglu S, Zhang X, Baader SL and Oberdick J. . 1998 J. Neurobiol. 36: 559–571.

  • Sauer F and Tjian R. . 1997 Curr. Opin. Genet. & Dev. 7: 176–181.

  • Schnabel CA and Abate-Shen C. . 1996 Mol. Cell. Biol. 16: 2678–2688.

  • Shen WF, Largman C, Lowney P, Corral JC, Detmer K, Hauser CA, Simonitch TA, Hack FM and Lawrence HJ. . 1989 Proc. Natl. Acad. Sci. USA 86: 8536–8540.

  • Shen WF, Montgomery JC, Rozenfeld S, Moskow JJ, Jeffrey Lawrence H, Buchberg AM and Largman C. . 1997 Mol. Cell. Biol. 17: 6448–6458.

  • Shikama N, Lyon J and La Thangue NB. . 1996 Trends Cell Biol. 7: 230–236.

  • Shimamoto T, Ohyashiki K, Toyama K and Takeshita K. . 1998 Int. J. Hematol. 67: 339–350.

  • Simeone A, Mavilio F, Acampora D, Giampaolo A, Paiella A, Zappavigna V, D'Esposito M, Pannese M, Russo G, Boncinelli E and Peschle C. . 1987 Proc. Natl. Acad. Sci. USA 84: 4914–4918.

  • Smith CL, Onate SA, Tsai MJ and O'Mailley BW. . 1996 Proc. Natl. Acad. Sci. USA 93: 8884–8888.

  • Sowa Y, Orita T, Minamikawa S, Nakano K, Mizuno T, Nomura H and Sakai T. . 1997 Biochem. Biophys. Res. Commun. 241: 142–150.

  • Tanaka Y, Naruse I, Maekawa T, Masuya H, Shiroishi T and Ishii S. . 1997 Proc. Natl. Acad. Sci. USA 94: 10215–10220.

  • Yang XJ, Ogryzko VV, Nishikawa JI, Howard BH and Nakatani Y. . 1996 Nature 382: 319–324.

  • Vigano MA, Di Rocco G, Zappavigna V and Mavilio F. . 1998 Mol. Cell. Biol. 18: 6201–6212.

  • Xu L, Lavinsky RM, Dasen JS, Flynn SE, McInerney EM, Mullen TM, Heinzel T, Szeto D, Korzus E, Kurokawa R, Aggarwal AK, Rose DW, Glass CK and Rosenfeld MG. . 1998 Nature 395: 301–306.

  • Zappavigna V, Sartori D and Mavilio F. . 1994 Genes Dev. 8: 732–744.

  • Zhang N, Shen WF, D Ho A and Lu M. . 1996 Oncogene 13: 1781–1787.

  • Zhang W and Bieker JJ. . 1998 Proc. Natl. Acad. Sci. USA 95: 9855–9860.

Download references

Acknowledgements

The authors are grateful to Dr Zappavigna for the gift of the pTCBS and pT109 plasmids, to Drs Kouzarides and Roeder for the GST-CBP plasmids and to Drs Evans and Montminy for the gift of both the CMX-CBP and the GAL4-CBP plasmids. V Bours and M-P Merville are Research Associates of the National Fund for Scientific Research (`FNRS', Belgium). A Chariot is a Research Assistant at the University of Liege and is supported by postdoctoral grants provided by both the NATO and the Fulbright Commission. This work was also supported by grants from the National Fund for Scientific Research. Télévie (Belgium) and the Centre Anti Cancéreux (University of Liège, Belgium).

Author information

Authors and Affiliations

  1. Laboratory of Medical Chemistry and Medical Oncology, CHU B35, University of Liege Sart-Tilman, Liege, 4000, Belgium

    Alain Chariot, Muriel Chapelier, Jacques Gielen, Marie-Paule Merville & Vincent Bours

  2. Department of Molecular Biology, Laboratory of Biological Chemistry, Free University of Brussels, Brussels, Belgium

    Carine van Lint

Authors
  1. Alain Chariot
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carine van Lint
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Muriel Chapelier
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jacques Gielen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marie-Paule Merville
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vincent Bours
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chariot, A., van Lint, C., Chapelier, M. et al. CBP and histone deacetylase inhibition enhance the transactivation potential of the HOXB7 homeodomain-containing protein. Oncogene 18, 4007–4014 (1999). https://doi.org/10.1038/sj.onc.1202776

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1202776

Keywords

Search

Advanced search

Quick links