Phosphorylated and hypoacetylated mutant p53 enhances cisplatin-induced apoptosis through caspase-9 pathway in the absence of transcriptional activation or translation

  • Authors:
    • Ming-Derg Lai
    • Wan-Chi Lin
    • Yih-Min Sun
    • Fu-Lin Chang
  • View Affiliations

  • Published online on: April 1, 2005     https://doi.org/10.3892/ijmm.15.4.725
  • Pages: 725-734
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Abstract

It is not completely understood how certain epithelial cells harboring mutant p53 have better response to chemotherapy. We investigate the mechanism of cisplatin-induced apoptosis in two resistant cell lines (parental TCCSUP and R273L mutant p53 transfectant) and two sensitive cell lines (V143A and N247I mutant p53 transfectants). Activation of caspase 9 was demonstrated by Western blotting, and specific inhibitor for caspase 9 could inhibit apoptosis. Inhibitors for caspases 1, 2, 6, and 8 had no effect on apoptosis. Transcriptional repression of Bcl-2 occurred during apoptosis and could be reversed by the treatment of histone deacetylase inhibitor trichostatin A (TSA). The expression of Noxa, p53 inducible ribonucleotide reductase subunit 2 (p53R2), and p53 inducible death domain (PIDD) gene were not elevated with treatment of cisplatin (CDDP). Surface trafficking of Fas or Fas-L was not observed. Ser15 of wild-type p53 and mutant p53 was phosphorylated in response to cisplatin. Acetylation of wild-type p53 increased, while acetylation of mutant p53 decreased during cisplatin treatment. Both transcriptional inhibitor actinomycin D and translational inhibitor cycloheximide did not inhibit apoptosis. These results indicated that phosphorylated and hypoacetylated mutant p53 could enhance cisplatin-induced apoptosis through activation of caspase 9 independent of transcriptional activation and translation.

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April 2005
Volume 15 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Lai M, Lin W, Sun Y and Chang F: Phosphorylated and hypoacetylated mutant p53 enhances cisplatin-induced apoptosis through caspase-9 pathway in the absence of transcriptional activation or translation. Int J Mol Med 15: 725-734, 2005.
APA
Lai, M., Lin, W., Sun, Y., & Chang, F. (2005). Phosphorylated and hypoacetylated mutant p53 enhances cisplatin-induced apoptosis through caspase-9 pathway in the absence of transcriptional activation or translation. International Journal of Molecular Medicine, 15, 725-734. https://doi.org/10.3892/ijmm.15.4.725
MLA
Lai, M., Lin, W., Sun, Y., Chang, F."Phosphorylated and hypoacetylated mutant p53 enhances cisplatin-induced apoptosis through caspase-9 pathway in the absence of transcriptional activation or translation". International Journal of Molecular Medicine 15.4 (2005): 725-734.
Chicago
Lai, M., Lin, W., Sun, Y., Chang, F."Phosphorylated and hypoacetylated mutant p53 enhances cisplatin-induced apoptosis through caspase-9 pathway in the absence of transcriptional activation or translation". International Journal of Molecular Medicine 15, no. 4 (2005): 725-734. https://doi.org/10.3892/ijmm.15.4.725