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  • Original Paper
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A novel protein, RTN-xS, interacts with both Bcl-xL and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity

Oncogene volume 19, pages 5736–5746 (2000)Cite this article

Abstract

Bcl-2 and Bcl-xL serve as critical inhibitors of apoptosis triggered by a broad range of stimuli, mainly acting on the mitochondria. We identified two members of the reticulon (RTN) family as Bcl-xL binding proteins, i.e., NSP-C (RTN1-C) and a new family member, RTN-xS, both of which did not belong to the Bcl-2 family and were predominantly localized on the endoplasmic reticulum (ER). RTN-xS interacted with both Bcl-xL and Bcl-2, increased the localization of Bcl-xL and Bcl-2 on the ER, and reduced the anti-apoptotic activity of Bcl-xL and Bcl-2. On the other hand, NSP-C interacted only with Bcl-xL, affected the localization of Bcl-xL, and reduced Bcl-xL activity, but had no effect on Bcl-2. These results suggest that RTN family proteins can modulate the anti-apoptotic activity of Bcl-xL and Bcl-2 by binding with them and can change their localization to the ER.

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Abbreviations

ER:

endoplasmic reticulum

mAb:

monoclonal antibody

pAb:

polyclonal antibody

TM:

tunicamycin

STS:

staurosporine

VDAC:

voltage-dependent anion channel

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Acknowledgements

We thank Dr Kudo for providing anti-presenilin-1 antibody. We also thank Mr Kawate and Dr Kashiwagi for help with the immunocytochemical studies. This work was supported in part by Grants-in-Aid for Scientific Research on Priority Areas and for COE Research from the Japanese Ministry of Education, Science, Sport and Culture.

The nucleotide sequences of the RTN-xL and RTN-xS have been submitted to the DDBJ/EMBL/GenBank (Accession No. AB040462 and AB040463, respectively).

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Authors and Affiliations

  1. Department of Medical Genetics, Biomedical Research Center, Osaka University Graduate School of Medicine, Osaka, Japan

    Shinji Tagami, Yutaka Eguchi, Manabu Kinoshita & Yoshihide Tsujimoto

  2. Department of Neuropsychiatry, Osaka University Graduate School of Medicine, Osaka, Japan

    Shinji Tagami & Masatoshi Takeda

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

    Shinji Tagami, Yutaka Eguchi & Yoshihide Tsujimoto

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Tagami, S., Eguchi, Y., Kinoshita, M. et al. A novel protein, RTN-xS, interacts with both Bcl-xL and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity. Oncogene 19, 5736–5746 (2000). https://doi.org/10.1038/sj.onc.1203948

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