Proteasomes act in the pre-mitochondrial signal transduction route towards roscovitine-induced apoptosis

  • Authors:
    • M. E.R. Henfling
    • F. C.S. Ramaekers
    • B. Schutte
  • View Affiliations

  • Published online on: November 1, 2004     https://doi.org/10.3892/ijo.25.5.1437
  • Pages: 1437-1446
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Abstract

The role of the ubiquitin-proteasome pathway during roscovitine induced apoptosis was evaluated in the non-small cell lung carcinoma cell line MR65. To this end specific inhibitors of proteasome activity, MG132 and lactacystin were used. Addition of MG132 or lactacystin, 1 h prior to the addition of the CDK-inhibitor roscovitine to the cell cultures inhibited apoptosis significantly, as measured by PS exposure, cytokeratin 18 cleavage and caspase-3 activation. Furthermore, we show that inhibition of proteasome activation prior to induction of apoptosis by roscovitine prevents loss of mitochondrial inner transmembrane potential (ΔΨm). In addition we found that MG132 and lactacystin prevent release of cytochrome c from the mitochondrion. In contrast to the above findings we see no effect of proteasome inhibition in Fas-mediated apoptosis. Taken together our data suggest a specific role for proteasomes very early in roscovitine-induced apoptosis, upstream from the caspase cascade and mitochondrion.

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November 2004
Volume 25 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Henfling ME, Ramaekers FC and Schutte B: Proteasomes act in the pre-mitochondrial signal transduction route towards roscovitine-induced apoptosis. Int J Oncol 25: 1437-1446, 2004.
APA
Henfling, M.E., Ramaekers, F.C., & Schutte, B. (2004). Proteasomes act in the pre-mitochondrial signal transduction route towards roscovitine-induced apoptosis. International Journal of Oncology, 25, 1437-1446. https://doi.org/10.3892/ijo.25.5.1437
MLA
Henfling, M. E., Ramaekers, F. C., Schutte, B."Proteasomes act in the pre-mitochondrial signal transduction route towards roscovitine-induced apoptosis". International Journal of Oncology 25.5 (2004): 1437-1446.
Chicago
Henfling, M. E., Ramaekers, F. C., Schutte, B."Proteasomes act in the pre-mitochondrial signal transduction route towards roscovitine-induced apoptosis". International Journal of Oncology 25, no. 5 (2004): 1437-1446. https://doi.org/10.3892/ijo.25.5.1437