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Caspase-mediated cleavage of p21Waf1/Cip1 converts cancer cells from growth arrest to undergoing apoptosis

Oncogene volume 18, pages 1131–1138 (1999)Cite this article

Abstract

The cyclin-dependent kinase inhibitor p21Waf1/Cip1 is a downstream effector of the p53-dependent cell growth arrest. We report herein that p21 was cleaved by caspase-3/CPP32 at the site of DHVD112↓L during the DNA damage-induced apoptosis of cancer cells. The cleaved p21 fragment could no more arrest the cells in G1 phase nor suppress the cells undergoing apoptosis because it failed to bind to the proliferating cell nuclear antigen (PCNA) and lost its capability to localize in the nucleus. Thus, caspase-3-mediated cleavage and inactivation of p21 protein may convert cancer cells from growth arrest to undergoing apoptosis, leading to the acceleration of chemotherapy-induced apoptotic process in cancer cells.

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Acknowledgements

This study was supported in part by a special grant for Advanced Research on Cancer, a Grant-in-Aid for Cancer Research from the Ministry of Education, Science and Culture of Japan, a grant from the Vehicle Racing Commemorative Foundation, and a grant from the Organization for Pharmaceutical Safety and Research (OPSR), Japan. During the review of this manuscript, Gervais et al. also reported that the p21 was cleaved by caspases during apoptosis induced by γ-irradiation (J Biol Chem, 273, 19207 – 19212, 1998).

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Authors and Affiliations

  1. Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, 113-0032, Tokyo

    Yongke Zhang, Naoya Fujita & Takashi Tsuruo

  2. Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 1-37-1, Kami-Ikebukuro, Toshimaku, 170-0012, Tokyo, Japan

    Takashi Tsuruo

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Zhang, Y., Fujita, N. & Tsuruo, T. Caspase-mediated cleavage of p21Waf1/Cip1 converts cancer cells from growth arrest to undergoing apoptosis. Oncogene 18, 1131–1138 (1999). https://doi.org/10.1038/sj.onc.1202426

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