Involvement of a p53-independent and post-transcriptional up-regulation for p21WAF/CIP1 following destabilization of the actin cytoskeleton

  • Authors:
    • Yi-Jang Lee
    • Cheng-Han Tsai
    • Jeng-Jong Hwang
    • Shu-Jun Chiu
    • Tzong-Jen Sheu
    • Peter C. Keng
  • View Affiliations

  • Published online on: February 1, 2009     https://doi.org/10.3892/ijo_00000184
  • Pages: 581-589
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Abstract

The tumor suppressor p21WAF/CIP1 mediates the proliferation arrest via p53-dependent or -independent gene transactivation following distinct environmental stresses. In this study, we show that direct destabilization of the actin cytoskeleton by actin-targeting reagents leads to a p53-independent up-regulation of p21WAF/CIP1. The actin-targeting agent cytochalasin B (10 µM) quickly disrupted the actin cytoskeleton of p53 wild-type and p53-null cells accompanied by up-regulation of p21WAF/CIP1. Nevertheless, both total p53 and ser-15 phosphorylated p53 were not accumulated concomitantly, compared to the effect caused by ionizing irradiation. P53-independent up-regulation of p21WAF/CIP1 was also observed by two other actin-targeting agents cytochalasin D and latrunculin B, but not by the microtubule inhibitor colcemid. Furthermore, we showed that p21WAF/CIP1 mRNA level was not increased, whereas the protein degradation was delayed. A reduction of ubiquitination for p21WAF/CIP1 protein was detected using immunoprecipitation/immunoblot analysis. Up-regulation of p21WAF/CIP1 was not associated with cytotoxicity induced by cytochalasin B that influenced DNA integrity and plating efficiency only after 24 h of treatment. In addition, up-regulated p21WAF/CIP1 was accompanied by reduction of phosphorylation on retinoblastoma (Rb) protein in p53-null cells, implying that p21WAF/CIP1 might in part account for the molecular regulation of cytochalasin B induced G1 phase arrest. Together, current results suggest that p21WAF/CIP1 level can be mediated by actin organization in the absence of p53 via a post-transcriptional machinery, and it may contribute to the growth ablation by agents targeting the actin cytoskeleton.

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February 2009
Volume 34 Issue 2

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

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APA
Lee, Y., Tsai, C., Hwang, J., Chiu, S., Sheu, T., & Keng, P.C. (2009). Involvement of a p53-independent and post-transcriptional up-regulation for p21WAF/CIP1 following destabilization of the actin cytoskeleton. International Journal of Oncology, 34, 581-589. https://doi.org/10.3892/ijo_00000184
MLA
Lee, Y., Tsai, C., Hwang, J., Chiu, S., Sheu, T., Keng, P. C."Involvement of a p53-independent and post-transcriptional up-regulation for p21WAF/CIP1 following destabilization of the actin cytoskeleton". International Journal of Oncology 34.2 (2009): 581-589.
Chicago
Lee, Y., Tsai, C., Hwang, J., Chiu, S., Sheu, T., Keng, P. C."Involvement of a p53-independent and post-transcriptional up-regulation for p21WAF/CIP1 following destabilization of the actin cytoskeleton". International Journal of Oncology 34, no. 2 (2009): 581-589. https://doi.org/10.3892/ijo_00000184