Ultraviolet-irradiation-induced apoptosis is mediated via ligand independent activation of tumor necrosis factor receptor 1 (original) (raw)

Oncogene volume 17, pages 2555–2563 (1998)Cite this article

Abstract

Ultraviolet (UV)-irradiation has been shown to induce jun N-terminal kinase activity via aggregation-mediated activation of tumor necrosis factor receptor 1 (TNFR1) but the role of TNFR1 in mediating UV-induced apoptosis has not been explored. Using p53-null cells, we demonstrate that UV-stimulated ligand independent activation of TNFR1 plays a major role in mediating the apoptotic effects of UV-irradiation. UV-irradiation and TNFα acted in a synergistic manner to induce apoptosis. UV-irradiation stimulated the aggregation-mediated activation of TNFR1 which was coupled with activation of caspase 8, the most proximal caspase in TNFα signaling pathway. CrmA and the dominant negative versions of FADD, caspase 8 and caspase 10, that block the apoptotic axis of TNFR1 at different levels, also independently inhibited the UV-induced apoptosis. The engagement of the membrane initiated events was specific for UV-irradiation since neither CrmA nor the dominant negative FADD, caspase 8 or caspase 10 blocked the ionizing radiation-induced apoptosis. Cisplatin and melphalan, the UV-mimetic agents known to elicit UV-type DNA damage, also induced apoptosis but differed from UV in that both of the former agents engaged the caspase cascade at a level distal to FADD. Consistent with these findings cisplatin also did not stimulate TNFR1 aggregation. Together these results indicate that DNA damage per se was not sufficient to activate the membrane TNFR1. Based on our results we propose that the plasma membrane initiated events play a predominant role in mediating UV-irradiation-induced apoptosis and that UV-irradiation appears to engage the apoptotic axis of TNFR1 and perhaps those of other membrane death receptors to transduce its apoptotic signals.

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Authors and Affiliations

  1. Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, 20892, Maryland, USA
    M Saeed Sheikh, Michael J Antinore & Albert J Fornace Jr
  2. Laboratory of Biological Chemistry, NIA, National Institutes of Health, Baltimore, 21224, Maryland, USA
    Ying Huang

Authors

  1. M Saeed Sheikh
  2. Michael J Antinore
  3. Ying Huang
  4. Albert J Fornace Jr

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Sheikh, M., Antinore, M., Huang, Y. et al. Ultraviolet-irradiation-induced apoptosis is mediated via ligand independent activation of tumor necrosis factor receptor 1.Oncogene 17, 2555–2563 (1998). https://doi.org/10.1038/sj.onc.1202292

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