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p73-alpha is capable of inducing scotin and ER stress

Oncogene volume 23, pages 3721–3725 (2004)Cite this article

Abstract

p73, like its family member p53, can induce programmed cell death following DNA damage. Here, we report that this mechanism also involves endoplasmic reticulum (ER) stress and the transactivation of scotin, a protein identified recently as a p53 target able to induce ER stress. By using Tet-On inducible cell lines (Saos 2 osteosarcoma cells that lack p53), we observed that TAp73α elicits significant alterations in the morphology of the ER system, namely in the fine subcellular localization of calnexin. We found that both TAp73α and p53 are strong inducers of scotin. On the other hand, the transcriptionally deficient short isoforms ΔNp73α did not upregulate the steady-state mRNA level of scotin, as evaluated by real-time RT–PCR. Following the induction of scotin, ER staining with calnexin showed evidence of morphological alteration, with variations in the intracellular concentration of free calcium, visualized by fluo-3 staining. The induction of ER stress by p73 was further supported by the transcriptional induction of Gadd 153, a transcription factor induced under ER stress conditions. In conclusion, the data reported indicate the ability of TAp73α and p53 (not ΔNp73α) to elicit scotin transactivation and ER stress. This molecular mechanism might contribute to the effector events inducing apoptosis downstream of p73.

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Acknowledgements

This work was supported by grants from Telethon (E1224), AIRC, EU (QLG1-1999-00739 and QLK-CT-2002-01956), MIUR, MinSan. MR is a recipient of an FIRC fellowship.

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Authors and Affiliations

  1. Department of Experimental Medicine and Biochemical Sciences, Biochemistry Laboratory, IDI-IRCCS, University of Rome ‘Tor Vergata’, Rome, 00133, Italy

    Alessandro Terrinoni, Marco Ranalli, Bruno Cadot & Gerry Melino

  2. Department of Pharmaco-biolology, University of Calabria, Cosenza, 87036, Italy

    Aida Leta & Giacinto Bagetta

  3. Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK

    Karen H Vousden

  4. Medical Research Council, Toxicology Unit, Hodgkin Building, Leicester University, PO Box 138, Lancaster Road, Leicester, LE1 9HN, UK

    Gerry Melino

  5. Via Montpellier 1, Rome, 00133, Italy

    Gerry Melino

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  1. Alessandro Terrinoni
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Correspondence to Gerry Melino.

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Terrinoni, A., Ranalli, M., Cadot, B. et al. p73-alpha is capable of inducing scotin and ER stress. Oncogene 23, 3721–3725 (2004). https://doi.org/10.1038/sj.onc.1207342

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