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Bcl-2/E1B 19 kDa-interacting protein 3-like protein (Bnip3L) interacts with Bcl-2/Bcl-xL and induces apoptosis by altering mitochondrial membrane permeability

Oncogene volume 18, pages 4523–4529 (1999)Cite this article

Abstract

We have previously reported on cloning of the human gene encoding Bcl-2/adenovirus E1B 19 kDa-interacting protein 3-like protein (Bnip3L) and its growth inhibitory effect on cancer cells. Here we show that Bnip3L contains a motif similar to the BH3 domain which is conserved in Bcl-2 family proteins as well as containing a membrane-anchoring domain, and that Bnip3L interacts with Bcl-2 and Bcl-xL. Immunofluorescence microscopy revealed that Bnip3L was localized in the mitochondria, when in the presence of the membrane-anchoring domain. Transient expression of Bnip3L induced apoptosis of Rat-1 and HeLa cells and mutational analysis revealed that the BH3 domain and the membrane-anchoring domain were required for Bnip3L to induce cell death. Addition of recombinant Bnip3L to isolated mitochondria induced membrane potential loss and cytochrome c release both of which have been suggested to be prerequisite for apoptotic cell death. These results suggest that Bnip3L is one of the BH3-containing pro-apoptotic proteins and that it targets the mitochondria when inducing apoptosis.

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Acknowledgements

This study was supported in part by a grant for Scientific Research on Priority Areas, by a grant for Center of Excellence Research, and by a grant for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan.

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Author notes

  1. Tsuneharu Miki

    Present address: Department of Urology, Kyoto Prefectural University of Medicine, Kajii-chou, Kawaramachi-dori-hirokoji-noboru, Kamigyou-ku, Kyoto, Kyoto, 602-0841, Japan

Authors and Affiliations

  1. Department of Medical Genetics, Biomedical Research Center, Osaka University Medical School, 2-2 Yamadaoka, Suita, 565-0871, Osaka, Japan

    Tetsuo Imazu, Shigeomi Shimizu, Shinji Tagami & Yoshihide Tsujimoto

  2. Department of Urology, Osaka University Medical School, 2-2 Yamadaoka, Suita, 565-0871, Osaka, Japan

    Tetsuo Imazu, Tsuneharu Miki & Akihiko Okuyama

  3. Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Japan

    Shigeomi Shimizu & Yoshihide Tsujimoto

  4. Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-0071, Japan

    Mieko Matsushima & Yusuke Nakamura

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Imazu, T., Shimizu, S., Tagami, S. et al. Bcl-2/E1B 19 kDa-interacting protein 3-like protein (Bnip3L) interacts with Bcl-2/Bcl-xL and induces apoptosis by altering mitochondrial membrane permeability. Oncogene 18, 4523–4529 (1999). https://doi.org/10.1038/sj.onc.1202722

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