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Prostate apoptosis response gene-4 sensitizes neoplastic lymphocytes to CD95-induced apoptosis

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Abstract

Evaluating the functional consequences of prostate apoptosis response gene-4 (par-4) expression in CD95-induced apoptosis of neoplastic lymphocytes, we demonstrate that par-4 increases apoptosis by upregulating the CD95 receptor on the cell surface and—with a concomitant decrease of the FLICE-like inhibitory protein (FLIP)—by promoting cleavage of the initiator caspases-8 and -10. This results in an enforced activation of the executioner caspases-6, -7, and -3 as well as in an activation of the mitochondrial pathway. Upon inhibition of caspase-8, overexpression of par-4 enables Jurkat cells to maintain a higher sensitivity to CD95-induced apoptosis by downregulating cIAP-2 and XIAP and by enforcing activation of the initiator caspase-10 as well as of the executioner caspases-6, -7, and -3.

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Abbreviations

7-AAD:

7-aminoactinomycin-D

IAP:

Inhibitor of apoptosis protein

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Acknowledgments

Supported by a grant from the Deutsche Jose-Carreras-Leukämiestiftung and by the Johann Wolfgang Goethe-University in Frankfurt, Germany. The experiments comply with the current laws of the country inclusive of ethic approval.

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Authors and Affiliations

  1. Department of Medicine III, Johann Wolfgang Goethe-University Hospital, Theodor-Stern-Kai-7, 60590, Frankfurt am Main, Germany

    Marion Bergmann, Natasa Kukoc-Zivojnov, Kai U. Chow, Bettina Trepohl, Dieter Hoelzer, Eckhart Weidmann, Paris S. Mitrou & Simone Boehrer

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  1. Marion Bergmann
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  2. Natasa Kukoc-Zivojnov
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  3. Kai U. Chow
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  4. Bettina Trepohl
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  5. Dieter Hoelzer
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  6. Eckhart Weidmann
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  7. Paris S. Mitrou
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  8. Simone Boehrer
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Correspondence to Simone Boehrer.

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Bergmann, M., Kukoc-Zivojnov, N., Chow, K.U. et al. Prostate apoptosis response gene-4 sensitizes neoplastic lymphocytes to CD95-induced apoptosis. Ann Hematol 83, 646–653 (2004). https://doi.org/10.1007/s00277-004-0922-3

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  • DOI: https://doi.org/10.1007/s00277-004-0922-3

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