PML isoforms IV and V contribute to adenovirus-mediated oncogenic transformation by functionally inhibiting the tumor-suppressor p53

P. Wimmer, J. Berscheminski, P. Blanchette, P. Groitl, P. E. Branton, R. T. Hay, T. Dobner, S. Schreiner (Lead / Corresponding author)

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    Abstract

    Although modulation of the cellular tumor-suppressor p53 is considered to have the major role in E1A/E1B-55K-mediated tumorigenesis, other promyelocytic leukemia nuclear body (PML-NB)/PML oncogenic domain (POD)-associated factors including SUMO, Mre11, Daxx, as well as the integrity of these nuclear bodies contribute to the transformation process. However, the biochemical consequences and oncogenic alterations of PML-associated E1B-55K by SUMO-dependent PML-IV and PML-V interaction have so far remained elusive. We performed mutational analysis to define a PML interaction motif within the E1B-55K polypeptide. Our results showed that E1B-55K/PML binding is not required for p53, Mre11 and Daxx interaction. We also observed that E1B-55K lacking subnuclear PML localization because of either PML-IV or PML-V-binding deficiency was no longer capable of mediating E1B-55K-dependent SUMOylation of p53, inhibition of p53-mediated transactivation or efficiently transforming primary rodent cells. These results together with the observation that E1B-55K-dependent SUMOylation of p53 is required for efficient cell transformation, provides evidence for the idea that the SUMO ligase activity of the E1B-55K viral oncoprotein is intimately linked to its growth-promoting oncogenic activities.Oncogene advance online publication, 16 March 2015; doi:10.1038/onc.2015.63.

    Original languageEnglish
    Pages (from-to)69-82
    Number of pages14
    JournalOncogene
    Volume35
    Early online date16 Mar 2015
    DOIs
    Publication statusPublished - 7 Jan 2016

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    Wimmer, P., Berscheminski, J., Blanchette, P., Groitl, P., Branton, P. E., Hay, R. T., Dobner, T., & Schreiner, S. (2016). PML isoforms IV and V contribute to adenovirus-mediated oncogenic transformation by functionally inhibiting the tumor-suppressor p53. Oncogene, 35, 69-82. https://doi.org/10.1038/onc.2015.63