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Autoamplification of apoptosis following ligation of CD95-L, TRAIL and TNF-α

Oncogene volume 19, pages 4255–4262 (2000)Cite this article

Abstract

CD95-L, TNF-α and TRAIL are death-inducing ligands (DILs) which may signal apoptosis via crosslinking of their cognate receptors. The present study shows that treatment of cells with agonistic mAB αAPO-1 (CD95), recombinant TRAIL or TNF-α leads to enhanced mRNA and protein expression of each DIL with concomitant death in target cells. Immunoprecipitation of CD95-L protein from supernatant as well as neutralizing antibodies suggest DIL proteins to be cooperatively acting mediators of these cytotoxic activity. Autoamplification of the death signal was blocked in cells with a defect in apoptosis signaling either due to a dysfunctional FADD molecule or to the failure to activate JNK/SAPKs. Phosphorylation and enhanced binding of cJun and ATF-2 to DIL promoters suggest JNK/SAPKs as activators of these transcription factors following death receptor triggering. In consequence, autocrine production of DILs allows the spread of death signals to sensitive target cells.

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Acknowledgements

We thank Dr B Baumann, Dr S Mariani, Dr P Roncaioli for helpful discussion, Dr I Jeremias for providing recombinant TRAIL protein, Dr V M Dixit for the gift of the BJAB cell line and A Frezza for excellent technical assistance.

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Authors and Affiliations

  1. Division of Pediatric Oncology, German Cancer Research Center, Heidelberg, Germany

    Ingrid Herr, Carsten Posovszky, Thomas Boehler & Klaus-Michael Debatin

  2. Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy

    Luisa Di Marzio & Maria Grazia Cifone

  3. University Children's Hospital, Ulm, Germany

    Klaus-Michael Debatin

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  1. Ingrid Herr
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  2. Carsten Posovszky
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Herr, I., Posovszky, C., Di Marzio, L. et al. Autoamplification of apoptosis following ligation of CD95-L, TRAIL and TNF-α. Oncogene 19, 4255–4262 (2000). https://doi.org/10.1038/sj.onc.1203776

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