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Role of caspases and possible involvement of retinoblastoma protein during TGFβ-mediated apoptosis of human B lymphocytes

Oncogene volume 18, pages 3511–3519 (1999)Cite this article

Abstract

In this study, we investigated the involvement of caspases in TGFβ-induced apoptosis in human B cells. Our results show that TGFβ-mediated nuclear fragmentation, observed in the Epstein – Barr virus-negative Burkitt's Lymphoma cell line BL41, was abolished in the presence of the tripeptide caspase inhibitor ZVAD-fmk or the specific caspase-3 inhibitor DEVD-fmk. Other apoptotic manifestations such as cell shrinkage, surface phosphatidylserine expression and chromatin condensation were strongly inhibited by ZVAD-fmk but only partially by DEVD-fmk. This suggests that other caspases in addition to caspase-3 control these apoptotis-associated features. Specific activation of caspase-3 during TGFβ-induced apoptosis was demonstrated by the DEVD-fmk-sensitive expression of the active p17 subunit of caspase-3 and by in vivo cleavage of PARP. In addition, TGFβ treatment of BL41 promoted the expression of both dephosphorylated and truncated forms of the retinoblastoma protein. Inhibition of caspase-3 activity abolished both nuclear fragmentation and expression of the truncated retinoblastoma protein, without modifying the G1 cell cycle arrest induced by TGFβ. Our data thus demonstrate that TGFβ-induced apoptosis of lymphoma B lymphocytes is dependent on caspase activation and involves caspase-dependent cleavage of the retinoblastoma protein.

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Acknowledgements

This work was supported by INSERM and grants from the Association pour la Recherche sur le Cancer (ARC, Villejuif, France) and the Ligue Nationale Contre Le Cancer. N Schrantz receives a fellowship from MESR (Ministère de l'Enseignement Supérieur et de la Recherche) and DA Blanchard from ARC.

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  1. Nicolas Schrantz and Dominique Alain Blanchard: N Schrantz and DA Blanchard contributed equally to this paper

Authors and Affiliations

  1. INSERM U.131-IPSC 32 rue des carnets, 92140 Clamart, France

    Nicolas Schrantz, Dominique Alain Blanchard, Marie-Thérèse Auffredou & Aimé Vazquez

  2. Centre Claude Bernard-CJF 95-2, 32 rue des carnets, 92140 Clamart, France

    Gérald Leca

  3. Department of Pediatrics, Women and Infant's Hospital of Rhode Island, Providence, Rhode Island, USA

    Surendra Sharma

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Schrantz, N., Blanchard, D., Auffredou, MT. et al. Role of caspases and possible involvement of retinoblastoma protein during TGFβ-mediated apoptosis of human B lymphocytes. Oncogene 18, 3511–3519 (1999). https://doi.org/10.1038/sj.onc.1202718

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