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Nuclear localization of Y-box factor YB1 requires wild-type p53

Oncogene volume 22, pages 2782–2794 (2003)Cite this article

Abstract

Nuclear localization and high levels of the Y-box binding protein YB1 appear to be important indicators of drug resistance and tumor prognosis. YB1 also interacts with the p53 tumor suppressor protein. In this paper, we explore a role for p53 in the nuclear localization of YB1. We report that various genotoxic stresses induce nuclear localization of YB1 in a small proportion of treated cells, but only in cells with wild-type p53. We go on to show directly that functional p53 is required for YB1 to translocate to the nucleus. Tumor-associated p53 mutants however are attenuated for YB1 nuclear localization as are mutants mutated in the proline-rich domain of p53. These data link the DNA-damage response of p53 to YB1 nuclear translocation. In addition, we find that YB1 inhibits p53-induced cell death and its ability to trans-activate promoters of genes involved in cell death signaling. Together these data suggest that some forms of p53 cause YB1 to accumulate in the nucleus, which in turn inhibits p53 activity. These results provide a possible explanation for the correlation of nuclear YB1 with drug resistance and poor prognosis in some tumor types, and for the first time implicate p53 in the process of nuclear translocation.

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Acknowledgements

We thank Moshe Oren (Rehovot) and Xin Lu (London) for plasmids. We also thank Kimitoshi Kohno (Kitakyushu) for antibody to YB1, Roger Reddel (Sydney) for IIICF/c cells, Mike Kastan (Johns Hopkins) for RKO cells and Bruce Baguley (Auckland) for amsacrine. This work was supported by grants from the Cancer Society and Health Research Council of New Zealand.

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  1. Pathology Department, Dunedin School of Medicine, University of Otago, Box 913, Dunedin, New Zealand

    You Fang Zhang, Craig Homer, Sara J Edwards, Lynne Hananeia, Janice Royds & Antony W Braithwaite

  2. Genesis Research and Development Corporation Limited, PO Box 50, Auckland, New Zealand

    Annette Lasham

  3. Physiology Department, School of Medical Sciences, University of Otago, Box 913, Dunedin, New Zealand

    Philip Sheard

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  1. You Fang Zhang
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Correspondence to Antony W Braithwaite.

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Zhang, Y., Homer, C., Edwards, S. et al. Nuclear localization of Y-box factor YB1 requires wild-type p53. Oncogene 22, 2782–2794 (2003). https://doi.org/10.1038/sj.onc.1206357

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