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Y-box factor YB1 controls p53 apoptotic function

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 have continued to explore YB1/p53 interactions. We report that transcriptionally active p53 is required for nuclear localization of YB1. We go on to show that nuclear YB1 regulates p53 function. Our data demonstrate that YB1 inhibits the ability of p53 to cause cell death and to transactivate cell death genes, but does not interfere with the ability of p53 to transactivate the CDKN1A gene, encoding the kinase p21WAF1/CIP1 required for cell cycle arrest, nor the MDM2 gene. We also show that nuclear YB1 is associated with a failure to increase the level of the Bax protein in normal mammary epithelial cells after stress activation of p53. Together these data suggest that (nuclear) YB1 selectively alters p53 activity, which may in part provide an explanation for the correlation of nuclear YB1 with drug resistance and poor tumor prognosis.

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Acknowledgements

This work was funded by the Cancer Society of New Zealand (Grant 99/11), the Health Research Council of New Zealand (Grant 04/234), and the New Zealand Lottery Board (Grant AP76795). We also thank Moshe Oren (Israel) and Karen Vousden (Scotland) for promoter-reporter constructs and Lily Huschtscha (Australia) for Bre-80 cells.

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Correspondence to Antony W Braithwaite.

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Homer, C., Knight, D., Hananeia, L. et al. Y-box factor YB1 controls p53 apoptotic function. Oncogene 24, 8314–8325 (2005). https://doi.org/10.1038/sj.onc.1208998

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Keywords

  • YB1
  • nuclear localization
  • p53 functions
  • apoptosis

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