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Caspase-mediated cleavage of cytoskeletal actin plays a positive role in the process of morphological apoptosis

Oncogene volume 18, pages 2423–2430 (1999)Cite this article

Abstract

Tumors result from the imbalance between cell growth and apoptosis. One of the characteristic changes in cancers is the abnormality in cytoskeleton, which suggests some roles of cytoskeletal proteins in tumorigenesis or the maintenance of tumor cells. Previously we showed that cytoskeletal actin is the substrate of caspases, the proteases responsible for apoptosis, while the role of actin cleavage in apoptosis remained unknown. To examine the cleavage of actin in vivo, we extensively performed immunoblot analysis using actin fragment-specific antibody. Here, we showed that, in some solid tumor cells, induction of apoptosis was accompanied by caspase-dependent actin-cleavage to 15 and 31 kDa fragments in vivo. To elucidate the role of actin-cleavage further, we introduced actin cleaved-fragments. We found that ectopic expression of an actin 15 kDa fragment induces morphological changes resembling those of apoptotic cells. The expression of the actin fragment induced a dramatic change of cellular actin localization, as visualized by enhanced green fluorescent protein (EGFP)-tagged actin, while the actin fragment expression did not cause caspase activation nor the cleavage of a marker substrate protein, poly (ADP-ribose) polymerase. These results indicate that actin cleavage could play a positive role in the morphological changes of apoptosis downstream of caspase activation.

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Acknowledgements

We are grateful to Drs Akihiro Tomida and Naoya Fujita for technical advice. We also thank Drs Shingo Dan, Naomi Haga and Zhihong Chen for helpful discussions. This work was supported by the Organization for Pharmaceutical Safety and Research (OPSR), Japan, Grants-in-Aid for Cancer Research and Scientific Research from the Ministry of Education, Science and Culture, and a grant from the Vehicle Racing Commemorative Foundation, Japan.

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Authors and Affiliations

  1. Laboratory of Biomedical Research, Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, 113, Japan

    Tetsuo Mashima, Mikihiko Naito & Takashi Tsuruo

  2. Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, 170, Japan

    Takashi Tsuruo

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  1. Tetsuo Mashima
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  2. Mikihiko Naito
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Mashima, T., Naito, M. & Tsuruo, T. Caspase-mediated cleavage of cytoskeletal actin plays a positive role in the process of morphological apoptosis. Oncogene 18, 2423–2430 (1999). https://doi.org/10.1038/sj.onc.1202558

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