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

• Published in: Oncogene Vol. 36; no. 45; pp. 6293 - 6305
• Main Authors: Li, Y, Wang, L, Liu, J, Zhang, P, An, M, Han, C, Guan, X, Zhang, K
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.11.2017; Nature Publishing Group
• Subjects: 13/1; 13/109; 13/2; 13/62; 38/1; 38/39; 38/61; 38/77; 38/89; 631/337/458/1524; 631/67/395; 82/1; 82/29; 82/83; Acylation; Apoptosis; Bmi protein; Care and treatment; Case-Control Studies; Cell Biology; Cell Line, Tumor; Cell self-renewal; Development and progression; DNA microarrays; Gene expression; Genetic aspects; Health aspects; Human Genetics; Humans; Immunoprecipitation; Internal Medicine; Male; Mass Spectrometry; Medicine; Medicine & Public Health; Mitogen-Activated Protein Kinase 7 - genetics; Mitogen-Activated Protein Kinase 7 - metabolism; N-Acetylglucosaminyltransferases - metabolism; O-GlcNAcylation; Oncogenes; Oncology; original-article; p53 Protein; Polycomb group proteins; Polycomb Repressive Complex 1 - genetics; Polycomb Repressive Complex 1 - metabolism; Post-translation; Prostate cancer; Prostatic Neoplasms - enzymology; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Protein Stability; Proteins; PTEN protein; Stem cells; Transcription; Transcription factors; Transfection; Tumorigenesis
• ISSN: 0950-9232; 1476-5594; 1476-5594
• DOI: 10.1038/onc.2017.223

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.