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Nrh, a human homologue of Nr-13 associates with Bcl-Xs and is an inhibitor of apoptosis

Oncogene volume 20, pages 5846–5855 (2001)Cite this article

Abstract

In search of human homologues of the anti-apoptotic protein Nr-13, we have characterized a human EST clone that potentially encodes a protein, which is the closest homologue of Nr-13 among the Bcl-2 family members, to date known, in humans. Phylogenetic analyses suggest Human nrh, Mouse diva/boo and Quail nr-13 to be orthologous genes. The nrh gene has the same overall organization as nr-13 and diva/boo with one single intron interrupting the ORF at the level of the Bcl-2-homology domain BH2. RT–PCR-based analysis of nrh expression indicated that this gene is preferentially expressed in the lungs, the liver and the kidneys. Interestingly, two in frame ATG codons can lead potentially to the synthesis of two products, one of them lacking 10 aminoacids at the N-terminal end. Sequence alignment with Nr-13 and Diva/Boo in addition to secondary structure prediction of the nrh transcript suggested that the shortest protein will be preferentially synthetized. Immunohistochemical analyses have revealed that Nrh is associated with mitochondria and the nuclear envelope. Moreover, Nrh preferentially associates with the apoptosis accelerator Bcl-Xs and behaves as an inhibitor of apoptosis both in yeast and vertebrate cells.

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Acknowledgements

Mrs J Bernaud has to be specially acknowledged for her help for FACS analysis and Dr A Coleman for critical reading of the manuscript. We thank Ms AL Nouvion for Western blotting analyses and Dr M Buisson, Dr P Colas, Dr S Korsmeyer, Dr I Mikealian, and Dr G Nunez for plasmids and antibodies. This work has been supported by grants from, Association pour la lutte Contre le Cancer (ARC), Fondation pour la Recherche Médicale, Ligue Nationale Contre le Cancer, Université Claude Bernard, Association Retina France and Fondation Singer-Polignac. A Aouacheria and E Arnaud are recipients of fellowships from the CNRS and Ligue Nationale Contre le Cancer (comité de la Haute Savoie) respectively.

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Author notes

  1. Abdel Aouacheria and Estelle Arnaud: A Aouacheria and E Arnaud contributed equally to this work

Authors and Affiliations

  1. Institut de Biologie et Chimie des Protéines, UMR 5086 CNRS/Université Claude Bernard, 7 passage du Vercors, F69367 Lyon cedex 07, France

    Abdel Aouacheria, Estelle Arnaud, Séverine Venet, Philippe Lalle & Germain Gillet

  2. Biométrie et Biologie Evolutive, UMR 5558 CNRS/Université Claude Bernard, 43 Boulevard du 11 novembre, Villeurbanne cedex, F69622, France

    Manolo Gouy

  3. Etablissement de Transfusion Sanguine, passage du Vercors, Lyon, F 69007, France

    Dominique Rigal

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Correspondence to Germain Gillet.

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Aouacheria, A., Arnaud, E., Venet, S. et al. Nrh, a human homologue of Nr-13 associates with Bcl-Xs and is an inhibitor of apoptosis. Oncogene 20, 5846–5855 (2001). https://doi.org/10.1038/sj.onc.1204740

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