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O-GlcNAcylation modulates Bmi-1 protein stability and potential oncogenic function in prostate cancer

Oncogene volume 36, pages 6293–6305 (2017)Cite this article

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Abstract

The Polycomb group transcriptional repressor Bmi-1 often overexpressed and participated in stem cells self-renewal and tumorigenesis initiating of prostate cancer. In this progression, Bmi-1 protein was regulated by transcription and post-translational modifications (PTMs). Nobly, the underlying PTMs regulation of Bmi-1 is poorly known. Here we use co-immunoprecipitation show that in C4-2 cell line, Bmi-1 directly interacted with OGT which is the only known enzyme catalyzed the O-GlcNAcylation in human. Furthermore, we identified that Ser255 is the site for Bmi-1 O-GlcNAcylation, and O-GlcNAcylation promoted Bmi-1 protein stability and its oncogenic activity. Finally, microarray analysis has characterized potential oncogenes associated pathway subject to repression via the OGT-Bmi-1 axis. Taken together, these results indicate that OGT-mediated O-GlcNAcylation at Ser255 stabilizes Bmi-1 and hence inhibits the TP53, PTEN and CDKN1A/CDKN2A pathway. The study not only uncovers a novel functional PTMs of Bmi-1 but also reveals a unique oncogenic role of O-GlcNAcylation in prostate cancer.

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Author notes

  1. Y Li and L Wang: These authors contributed equally to this work.

Authors and Affiliations

  1. Sino-UK Regenerative Medicine Center, the First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China

    Y Li, L Wang, J Liu, M An, C Han, Y Li & X Guan

  2. Department of Pathology, the First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China

    P Zhang

  3. Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA

    K Zhang

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  1. Y Li
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Correspondence to J Liu.

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Li, Y., Wang, L., Liu, J. et al. O-GlcNAcylation modulates Bmi-1 protein stability and potential oncogenic function in prostate cancer. Oncogene 36, 6293–6305 (2017). https://doi.org/10.1038/onc.2017.223

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