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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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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DOI: https://doi.org/10.1038/sj.onc.1203948
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