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Genotoxic stress-induced nuclear localization of oncoprotein YB-1 in the absence of proteolytic processing

Oncogene volume 29, pages 403–410 (2010)Cite this article

Abstract

Y-box-binding protein 1 (YB-1) is an oncogenic transcription factor whose overexpression and nuclear localization is associated with tumor progression and drug resistance. Transcriptional activation of YB-1 in response to genotoxic stress is believed to occur in the cytoplasm through sequence-specific endoproteolytic cleavage by the 20S Proteasome, followed by nuclear translocation of cleaved YB-1. To study the proteolysis model, we developed a two-step affinity purification of endogenous YB-1 protein species and characterized the products using mass spectrometry. Whereas full-length YB-1 was readily identified, the smaller protein band thought to be activated YB-1 was identified as hnRNP A1. An antibody specific for YB-1 was generated, which revealed only one YB-1 species, even after genotoxic stress-induced nuclear YB-1 translocation. These findings warrant re-evaluation of the mechanism of YB-1 nuclear translocation and transcriptional activation. The relationship between nuclear YB-1 and tumor progression may also have to re-evaluated in some cases.

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Acknowledgements

We thank Professor H-D Royer (CASEAR, Bonn, Germany) for a generous gift of the C-terminal YB-1 antibody. This research was supported by the National Health & Medical Research Council of Australia (SBC, 423405; PJP, 477100), the Cancer Institute NSW (AWB, WM, 05/RLP/1-01), the Health Research Council of New Zealand (AWB, AMW, RH, MA 07/284A) and the Children's Medical Research Institute Jeans-for-Genes Campaign (VAV).

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Author notes

  1. S B Cohen, W Ma and V A Valova: These authors contributed equally to this work.

Authors and Affiliations

  1. Cell Transformation Unit, Children's Medical Research Institute, Westmead, New South Wales, Australia

    S B Cohen, W Ma & A W Braithwaite

  2. Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia

    S B Cohen, P J Robinson & A W Braithwaite

  3. Cell Signalling Unit, Children's Medical Research Institute, Westmead, New South Wales, Australia

    V A Valova & P J Robinson

  4. Department of Pathology, Cell Transformation Group, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand

    M Algie, R Harfoot, A G Woolley & A W Braithwaite

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  1. S B Cohen
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  3. V A Valova
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Correspondence to A W Braithwaite.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Cohen, S., Ma, W., Valova, V. et al. Genotoxic stress-induced nuclear localization of oncoprotein YB-1 in the absence of proteolytic processing. Oncogene 29, 403–410 (2010). https://doi.org/10.1038/onc.2009.321

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