O-GlcNAcylation modulates Bmi-1 protein stability and potential oncogenic function in prostate cancer
O-GlcNAcylation modulates Bmi-1 protein stability and potential oncogenic function in prostate cancer
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O-GlcNAcylation 调节 Bmi-1 蛋白稳定性和前列腺癌中的潜在致癌功能
DOI：
10.1038/onc.2017.223
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发表时间：
2017-11-09
期刊：
影响因子：
8
通讯作者：
Zhang, K.
中科院分区：
文献类型：
--
作者：
Li, Y.;Wang, L.;Zhang, K.
Polycomb组转录抑制因子Bmi-1常过表达，参与干细胞自我更新和前列腺癌的发生。在此过程中，Bmi-1蛋白受到转录和翻译后修饰（PTM）的调控。值得注意的是，Bmi-1的潜在PTM调控知之甚少。本研究利用免疫共沉淀技术，在C4-2细胞株中，Bmi-1与OGT直接相互作用，OGT是目前已知的唯一一种催化O-GlcNAc化的酶。此外，我们还发现Ser 255是Bmi-1的O-GlcNAc基化位点，O-GlcNAc基化促进了Bmi-1蛋白的稳定性和致癌活性。最后，微阵列分析表征了通过OGT-Bmi-1轴受到抑制的潜在癌基因相关途径。综上所述，这些结果表明，OGT介导的Ser 255处的O-GlcNAc化稳定Bmi-1，从而抑制TP 53、PTEN和CDKN 1A/CDKN 2A途径。该研究不仅揭示了Bmi-1的新功能性PTM，而且还揭示了O-GlcNAc化在前列腺癌中的独特致癌作用。
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.