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Acinus is a caspase-3-activated protein required for apoptotic chromatin condensation

Nature volume 401, pages 168–173 (1999)Cite this article

Abstract

Apoptosis is defined by several unique morphological nuclear changes, such as chromatin condensation and nuclear fragmentation1. These changes are triggered by the activation of a family of cysteine proteases called caspases2,3, and caspase-activated DNase (CAD/DFF40)4,5 and lamin protease (caspase-6)6,7 have been implicated in some of these changes. CAD/DFF40 induces chromatin condensation in purified nuclei, but distinct caspase-activated factor(s) may be responsible for chromatin condensation8. Here we use an in vitro system to identify a new nuclear factor, designated Acinus, which induces apoptotic chromatin condensation after cleavage by caspase-3 without inducing DNA fragmentation. Immunodepletion experiments showed that Acinus is essential for apoptotic chromatin condensation in vitro, and an antisense study revealed that Acinus is also important in the induction of apoptotic chromatin condensation in cells.

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Figure 1: Purification of an apoptotic chromatin-condensation factor from bovine thymus.
Figure 2: Primary structure of Acinus, and cleavage of Acinus by caspase-3.
Figure 3: Induction of chromatin condensation in permeabilized cell nuclei by recombinant Acinus, and nuclear localization of Acinus.
Figure 4: Role of Acinus for chromatin condensation in vitro.
Figure 5: Role of Acinus for apoptotic chromatin condensation in cells.

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Acknowledgements

We thank O. Ohara and J. Miyazaki for KIAA0670 plasmid and pCAGGS plasmid, respectively, and Y. Sakamoto for help with microsequence analysis. This work was supported in part by grants for Scientific Research on Priority Areas, for COE Research, and for JSPS fellows from the Ministry of Education, Science, Sports and Culture of Japan.

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Authors and Affiliations

  1. Department of Medical Genetics, Biomedical Research Center,

    Setsuko Sahara, Mamoru Aoto, Yutaka Eguchi & Yoshihide Tsujimoto

  2. Department of Anatomy and Cell Biology, Osaka University Medical School,

    Naoko Imamoto & Yoshihiro Yoneda

  3. CREST of Japan Science and Technology Corporation (JST), 2-2 Yamadaoka, Suita, Osaka, 565–0871, Japan

    Setsuko Sahara, Mamoru Aoto, Yutaka Eguchi & Yoshihide Tsujimoto

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  1. Setsuko Sahara
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Correspondence to Yoshihide Tsujimoto.

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Sahara, S., Aoto, M., Eguchi, Y. et al. Acinus is a caspase-3-activated protein required for apoptotic chromatin condensation. Nature 401, 168–173 (1999). https://doi.org/10.1038/43678

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