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Transformation, genomic instability and senescence mediated by platelet/megakaryocyte glycoprotein Ibα

Oncogene volume 27, pages 1599–1609 (2008)Cite this article

16 February 2021 EDITOR’S NOTE: Readers are alerted that in Figure 4G, the p53-shRNA and Gplbα+p53-shRNA appear to be duplicates. As this research was performed many years ago, the authors do not have the original data. However, it does not appear that these duplications affect the overall conclusions of the article.

Abstract

GpIbα, a subunit of the von Willebrand factor receptor, functions during blood clotting to promote platelet adhesion and activation. GpIbα is widely expressed, is positively regulated by c-Myc and is essential for the promotion of c-Myc-mediated chromosomal instability. We now show that GpIbα is also a classical oncoprotein in which its deregulated expression leads to transformation, reduced growth factor requirements, increased resistance to apoptosis, and, in primary cells, p53-dependent senescence. Finally, GpIbα also promotes double-stranded DNA breaks, and induces profound nuclear dysmorphology, indicating that, in addition to its direct transforming function, it displays genotoxicity at several distinct levels. These findings identify novel functions for GpIbα and pathways through which c-Myc mediates transformation and global genomic destabilization.

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  • 16 February 2021

    EDITOR’S NOTE: Readers are alerted that in Figure 4G, the p53-shRNA and Gplbα+p53-shRNA appear to be duplicates. As this research was performed many years ago, the authors do not have the original data. However, it does not appear that these duplications affect the overall conclusions of the article.

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Acknowledgements

We thank Reuven Agami for pSUPER-shp53 vector and Bill Saunders for valuable discussions. This work was supported by NIH grants RO1CA078259 and RO1 CA105033 to EVP and by a Children's Hospital of Pittsburgh Research Advisory Committee postdoctoral fellowship award to YL.

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Authors and Affiliations

  1. Section of Hematology/Oncology, Rangos Research Center, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA

    Y Li, J Lu, D Cohen & E V Prochownik

  2. Department of Molecular Genetics and Biochemistry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    E V Prochownik

  3. University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    E V Prochownik

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Correspondence to E V Prochownik.

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

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Li, Y., Lu, J., Cohen, D. et al. Transformation, genomic instability and senescence mediated by platelet/megakaryocyte glycoprotein Ibα. Oncogene 27, 1599–1609 (2008). https://doi.org/10.1038/sj.onc.1210794

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