Skip to main content
SpringerLink
Log in

Bax deficiency affects caspase-2 activation during ultraviolet radiation-induced apoptosis

  • Short Report
  • Published:
Oncogene Submit manuscript

Abstract

There has been a considerable debate as to whether caspase-2 is an initiator or effector caspase. Recently, a new model of intrinsic pathway of apoptosis has been proposed, which suggests caspase-2 to be an initiator caspase. For example, ultraviolet radiation (UV) and other DNA damage-inducing agents were shown to first activate caspase-2 and then regulate the mitochondrial and postmitochondrial events. Active caspase-2 was found to engage mitochondria by promoting Bax translocation to the mitochondria. Consequently, Bax was proposed to play a central role in bridging the active caspase-2 with mitochondria by affecting mitochondrial permeability, cytochrome c release into the cytosol and caspase-9 activation. In the present study, we investigated the role of Bax in UV-induced apoptosis and caspase-2 activation. Our results indicate that UV-induced apoptosis and caspase-2 activation were diminished in Bax-deficient cells, suggesting that Bax appears to play an important role in UV-induced apoptosis as well as caspase-2 activation, and that it also appears to reside upstream of caspase-2. Bax deficiency also affected the activation of caspase-3 and -8 and abolished caspase-9 activation during UV-induced apoptosis, suggesting that the absence of caspase-9 activation may affect caspase-2, -3 and -8 activation in Bax-deficient cells. Based on our results, we propose that activation of caspases is not a linear cascade of events, but is rather connected via complex feedback loops.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  • Aragane Y, Klums D, Metze D, Wikes G, Poppelmann B, Luger TA and Schwarz T . (1998). J. Cell Biol., 140, 171–182.

  • Ashkenazi A and Dixit VM . (1999). Curr. Opin. Cell Biol., 11, 255–260.

  • Cowling V and Downward J . (2002). Cell Death Differ., 9, 1046–1056.

  • Fujita E, Egashira J, Urase K, Kuida K and Momoi T . (2001). Cell Death Differ., 8, 335–344.

  • Gross A, McDonnell JM and Korsmeyer SJ . (2000). Genes Dev., 13, 1899–1911.

  • Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T and Alnemri ES . (2002). J. Biol. Chem., 277, 13430–134307.

  • Harvey NL, Butt AJ and Kumar S . (1997). J. Biol. Chem., 272, 13134–13139.

  • He Q, Luo X, Huang Y and Sheikh MS . (2002). Oncogene, 21, 6032–6040.

  • Hengartner MO . (2000). Nature, 407, 770–776.

  • Holcik M and Korneluk RG . (2001). Nat. Rev. Mol. Cell Biol., 2, 550–556.

  • Huang Y, He Q, Hillman MJ, Rong R and Sheikh MS . (2001). Cancer Res., 61, 6918–6924.

  • 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.

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

  • Rehemtulla A, Hamilton CA, Chinnaiyan AM and Dixit VM . (1997). J. Biol. Chem., 272, 25783–257836.

  • Robertson JD, Enoksson M, Suomela M, Zhivotovsky B and Orrenius S . (2002). J. Biol. Chem., 2002277, 29803–29809.

  • Schulze-Osthoff K, Ferrari D, Los M, Wesselborg S and Peter ME . (1998). Eur. J. Biochem., 254, 439–459.

  • Sheikh MS, Antinore MJ, Huang Y and Fornace Jr AJ . (1998). Oncogene, 17, 2555–2563.

  • Sheikh MS and Fornace Jr AJ . (2000). J. Cell. Physiol., 182, 171–181.

  • Sitailo LA, Tibudan SS and Denning MF . (2002). J. Biol. Chem., 277, 19346–19352.

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

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

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

  • Wang X . (2001). Genes Dev., 15, 2922–2933.

  • Zhang L, Yu J, Park BH, Kinzler KW and Vogelstein B . (2000). Science, 290, 989–992.

Download references

Acknowledgements

We thank Dr Bert Vogelstein (Johns Hopkins University, Baltimore, MD), for kindly providing the Bax-proficient and -deficient cells used in this study. This work was supported in part by NIH grants CA89043, CA86945 and a Department of Defense grant DMAD 170010722.

Author information

Authors and Affiliations

  1. Department of Pharmacology, State University of New York, Upstate Medical University, 750 E Adams Street, Syracuse, 13210, NY, USA

    Qin He, Ying Huang & M Saeed Sheikh

Authors
  1. Qin He
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ying Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Saeed Sheikh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M Saeed Sheikh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

He, Q., Huang, Y. & Sheikh, M. Bax deficiency affects caspase-2 activation during ultraviolet radiation-induced apoptosis. Oncogene 23, 1321–1325 (2004). https://doi.org/10.1038/sj.onc.1207212

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1207212

  • Springer Nature Limited

Keywords

This article is cited by

Search

Navigation