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PA26, a novel target of the p53 tumor suppressor and member of the GADD family of DNA damage and growth arrest inducible genes

Oncogene volume 18, pages 127–137 (1999)Cite this article

Abstract

Exposure of mammalian cells to hypoxia, radiation and certain chemotherapeutic agents promotes cell cycle arrest and/or apoptosis. Activation of p53 responsive genes is believed to play an important role in mediating such responses. In this study we identified a novel gene, PA26, which maps to chromosome 6q21 and encodes at least three transcript isoforms, of which two are differentially induced by genotoxic stress (UV, γ-irradiation and cytotoxic drugs) in a p53-dependent manner. A functional p53-responsive element was identified in the second intron of the PA26 gene, in consistence with a mechanism of transcriptional induction of the PA26 gene by p53. No clues to its functions were revealed by sequence analysis, although pronounced negative regulation by serum factors argues for a potential role of PA26 in growth regulation. Immunological analysis suggests that PA26 protein(s) is localized to the cell nucleus. Our results suggest that the PA26 gene is a novel p53 target gene with properties common to the GADD family of growth arrest and DNA damage-inducible stress-response genes, and, thus, a potential novel regulator of cellular growth.

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Acknowledgements

The authors would like to acknowledge Xavier Villareal for sequencing and suggestions with RTPCR analysis. The authors also acknowledge Wily Kratil and Jose Alcantara for their assistance with graphics. The gifts of EB-1 cells by Dr P Shaw (CHUV, Lausanne) and RKO cells by Dr M Kastan (Johns Hopkins University) are gratefully acknowledged.

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Authors and Affiliations

  1. Department of Oncology, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, 08543, New Jersey, USA

    Susana Velasco-Miguel, Leonard Buckbinder, Patrice Jean, Larry Gelbert, Randy Talbott, Jana Laidlaw, Bernd Seizinger & Nikolai Kley

  2. Pfizer Central Research, Box 51, Groton, 06340, Connecticut, USA

    Leonard Buckbinder

  3. Department of Molecular Biology, Princeton University, Princeton, 08543, New Jersey, USA

    Patrice Jean

  4. Genome Therapeutics Corporation, Waltham, 02154, Massachusetts, USA

    Bernd Seizinger & Nikolai Kley

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  1. Susana Velasco-Miguel
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Velasco-Miguel, S., Buckbinder, L., Jean, P. et al. PA26, a novel target of the p53 tumor suppressor and member of the GADD family of DNA damage and growth arrest inducible genes. Oncogene 18, 127–137 (1999). https://doi.org/10.1038/sj.onc.1202274

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