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.

  • Oncogenomics
  • Published:

The human caspase-2 gene: alternative promoters, pre-mRNA splicing and AUG usage direct isoform-specific expression

Oncogene volume 22, pages 935–946 (2003)Cite this article

Abstract

Caspases have been shown to play important roles in apoptotic cell death, cytokine maturation and cell differentiation. However, the transcriptional regulation of the corresponding CASP genes remains poorly known. We describe a 5.1 kb fragment located upstream of the first translated exon in the human CASP-2 gene, which is known to encode caspase-2L and -2S protein isoforms. Transient transfection experiments, together with transcription start site mapping and transcript analysis, demonstrate that each caspase mRNA is initiated from separate promoter regions, and produced from alternative splicing events in these regions. The CASP-2L promoter is much stronger than the CASP-2S promoter, in good agreement with the respective transcript levels of the two caspases. In addition, several in-frame translational start sites can be identified for each isoform, one of which is common to both, present in the second common exon, and used efficiently. Surprisingly, the short isoform may also be initiated at a downstream AUG codon within the same exon. Thus, promoter strength, alternative transcriptional initiation and 5′-splicing events regulate the expression of the main caspase-2 isoforms that may be translated from alternative translation initiation codons.

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

Similar content being viewed by others

References

  • Ahmad M, Srinivasula SM, Wang L, Talaniann RV, Litwack G, Fernandes-Alnemri T and Alnemri ES . (1997). Cancer Res., 4, 615–619.

  • Allet B, Hochmann A, Martinou I, Berger A, Missotten M, Antonsson B, Sadoul R, Martinou JC and Bernasconi L . (1996). J. Cell. Biol., 135, 479–486.

  • Alnemri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA, Wong WW and Yuan J (1996). Cell, 87, 171.

  • Asahi M, Hoshimaru M, Uemura Y, Tokime T, Kojima M, Ohtsuka T, Matsuura N, Aoki T, Shibahara K and Kikuchi H . (1997). J. Cereb. Blood Flow Metab., 17, 11–18.

  • Bergeron L, Perez GI, Macdonald G, Shi L, Sun Y, Juriscova A, Varmuza S, Latham KE, Flaws JA, Salter JC, Hara H, Moskowitz MA, Li E, Greenberg A, Tilly JL and Yuan J . (1998). Genes Dev., 12, 1304–1314.

  • Boise LH, Gonzalez-Garcia M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nunez G and Thompson CB . (1993). Cell, 74, 597–608.

  • Bonfoco E, Li E, Kolbinger F and Cooper NR . (2001). J. Biol. Chem., 276, 29242–29250.

  • Butt AJ, Harvey NL, Parasivam G and Kumar S . (1998). J. Biol. Chem., 273, 6763–6768.

  • Colussi PA, Harvey NL and Kumar S . (1998a). J. Biol. Chem., 273, 24535–24542.

  • Colussi P, Harvey NL, Shearwin-Whyatt LM and Kumar S . (1998b). J. Biol. Chem., 273, 26566–26570.

  • Cote J, Dupuis S, Jiang Z and Wu JY . (2001a). Proc. Natl. Acad. Sci. USA, 98, 938–943.

  • Cote J, Dupuis S and Wu JY . (2001b). J. Biol. Chem. 276, 8535–8543.

  • Droin N, Beauchemin M, Solary E and Bertrand R . (2000). Cancer Res., 60, 7039–7047.

  • Droin N, Bichat F, Rebe C, Wotawa A, Sordet O, Hamman A, Bertrand R and Solary E . (2001a). Blood, 97, 1835–1844.

  • Droin N, Dubrez L, Eymin B, Renvoize C, Breard J, Dimanche-Boitrel MT and Solary E . (1998). Oncogene, 16, 2885–2894.

  • Droin N, Rebe C, Bichat F, Hammann A, Bertrand R and Solary E . (2001b). Oncogene 20, 260–269.

  • Duan H and Dixit VM . (1997). Nature 385, 86–89.

  • Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T and Alnemri ES . (2002). J. Biol. Chem., 277, 13430–13437.

  • Harvey N, Trapani JA, Fernandes-Alnemri T, Litwack G, Alnemri ES and Kumar S . (1996). Genes Cells, 1, 673–685.

  • Ito A, Uehara T and Nomura Y . (2000). FEBS Lett., 470, 360–364.

  • Jiang ZH and Wu JY . (1999). Proc. Soc. Exp. Biol. Med., 220, 64–72.

  • Kojima M, Asahi M, Kikuchi H, Hashimoto N, Noda M and Hoshimaru M . (1998). Neurosci. Res., 31, 211–217.

  • Kozak C . (1986). Cell, 44, 283–292.

  • Kumar S . (1995). FEBS Lett., 368, 69–72.

  • Kumar S, Kinoshita M and Noda M . (1997). Leukemia, 11, S3: 385–386.

  • Kumar S, Kinoshita M, Noda M, Copeland NG and Jenkins NA . (1994). Genes Dev., 8, 1613–1626.

  • Kumar S, Tomooka Y and Noda M . (1992). Biochem. Biophys. Res. Commun., 185, 1155–1161.

  • Lassus P, Opitz-Araya X and Lazebnik Y . (2002). Science, 297, 1352–1354.

  • Li H, Bergeron L, Cryns V, Pasternack MS, Zhu H, Shi L, Greenberg A and Yuan J . (1997). J. Biol. Chem., 272, 21010–21017.

  • Liu W, Wang G and Yakovlev AG . (2002). J. Biol Chem., 277, 8273–8278.

  • Mancini M, Machamer CE, Roy S, Nicholson DW, Thornberry NA, Casciola-Rosen LA and Rosen A . (2000). J. Cell Biol., 149, 603–612.

  • Mendelsohn AR, Hamer JD, Wang ZB and Brent R . (2002). Proc. Natl. Acad. Sci. USA, 99, 6871–6876.

  • Micheau O, Solary E, Hammann A and Dimanche-Boitrel MT . (1999). J. Biol. Chem., 274, 7987–7992.

  • Morita Y, Maravei DV, Bergeron L, Wang S, Perez GI, Tsutsumi O, Taketani Y, Asano M, Horai R, Korsmeyer SJ, Iwakura Y, Yuan J and Tilly JL . (2001). Cell Death Differ., 8, 614–620.

  • Nicholson DW . (1999). Cell Death Differ., 6, 1028–1042.

  • Nishiyama J, Yi X, Venkatachalam MA and Dong Z . (2001). Biochem. J., 360, 49–56.

  • Paroni G, Henderson C, Schneider C and Brancolini C . (2001). J. Biol. Chem., 276, 21907–21915.

  • Paroni G, Henderson C, Schneider C and Brancolini C . (2002). J. Biol. Chem. 277, 15147–15161.

  • Pecci A, Viegas LR, Baranao JL and Beato M . (2001). J. Biol. Chem., 276, 21062–61069.

  • Robertson JD, Enoksson M, Suomela M, Zhivotovsky B and Orrenius S . (2002). J. Biol. Chem., 277, 29803–29809.

  • Sato N, Milligan CE, Uchiyama Y and Oppenheim RW . (1997). Gene, 202, 127–132.

  • Shikama Y, Mami U, Miyashita T and Yamada M . (2001). Exp. Cell Res., 264, 315–325.

  • Slee EA, Harte MT, Kluck RM, Wolf B, Casiano CA, Newmeyer DD, Wang HG, Reed JC, Nicholsmon DW, Alnemri ES, Green DR and Martin SJ . (1999). J. Cell. Biol., 144, 281–292.

  • Sordet O, Rebe C, Dubrez-Daloz L, Boudard D and Solary E . (2002). Leukemia, 16, 1569–1570.

  • Stefanis L, Troy CM, Qi H, Shelanski ML and Greene LA . (1998). J. Neurosci., 18, 9204–9215.

  • Susin SA, Lorenzo HK, Zamzami N, Marzo I, Brenner C, Larochette N, Prevost MC, Alzari PM and Kroemer G . (1999). J. Exp. Med., 189, 381–394.

  • Swanton E, Savory P, Cosulich S, Clarke P and Woodman P . (1999). Oncogene 18, 1781–1787.

  • Thornberry NA, Rano TA, Peterson EP, Rasper DM, Timkey T, Garcia-Calvo M, Houtzager VM, Nordstrom PA, Ro S, Vaillancourt JP, Chapman KT and Nicholson DW . (1997). J. Biol. Chem, 272, 17907–17911.

  • Thornberry NA and Lazebnik Y . (1998). Science, 281, 1312–1316.

  • Troy CM, Rabacchi SA, Friedman WJ, Frappier TF, Brown K and Shelanski ML . (2000). J. Neurosci., 20, 1386–1392.

  • Wang L, Miura M, Bergeron L, Zhu H and Yuan J . (1994). Cell, 78, 739–750.

  • Willis AE . (1999). Int. J. Biochem. Cell. Biol., 31, 73–86.

  • Wotawa A, Solier S, Logette E, Solary E and Corcos L . (2002). Cancer Lett., 185, 181–189.

Download references

Acknowledgements

We thank members from the Inserm U517 for numerous encouraging discussions. E Logette and S Solier were recipients at fellowships from the French Ministry of Research and Technology and from the Medical Research Foundation, respectively. This work was supported by grants from the Inserm, the Ligue Nationale Française de la Recherche Centre le Cancer and the Conseil Regional de Bourgogne.

Author information

Authors and Affiliations

  1. Inserm U517, Faculty of Medicine, 7 Bd Jeanne d'Arc, Dijon, 21000, France

    Emmanuelle Logette, Anne Wotawa, Stéphanie Solier, Lydie Desoche, Eric Solary & Laurent Corcos

Authors
  1. Emmanuelle Logette
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anne Wotawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stéphanie Solier
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lydie Desoche
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eric Solary
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Laurent Corcos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Laurent Corcos.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Logette, E., Wotawa, A., Solier, S. et al. The human caspase-2 gene: alternative promoters, pre-mRNA splicing and AUG usage direct isoform-specific expression. Oncogene 22, 935–946 (2003). https://doi.org/10.1038/sj.onc.1206172

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206172

Keywords

This article is cited by

Search

Advanced search

Quick links