Modification of p27 With O-Linked N-Acetylglucosamine Regulates Cell Proliferation in Hepatocellular Carcinoma
Modification of p27 With O-Linked N-Acetylglucosamine Regulates Cell Proliferation in Hepatocellular Carcinoma
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DOI：
10.1002/mc.22490
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发表时间：
2017
影响因子：
4.6
通讯作者：
Aiguo Shen
中科院分区：
文献类型：
--
作者：
Huiyuan Qiu;Fang Liu;Tao Tao;Dongmei Zhang;Xiaojuan Liu;Guizhou Zhu;Zhiwei Xu;Runzhou Ni;Aiguo Shen
The tumor suppressor p27, which is a member of the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins.(CKIs), controls anti-proliferative events. The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC.(hepatocellular carcinoma) cell lines, and we identifi ed Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites.of p27 based on the Q-TOF spectrum. Here, immunoprecipitation analysis showed that Ser2 was O-GlcNAcylated and that.this modifi cation was associated with the increased phosphorylation of p27 at Ser10, ultimately resulting in p27.accumulation in the cytoplasm and increased p27 ubiquitination. In addition, O-GlcNAcylation at Ser2 suppressed Cyclin/.CDK complex-p27 interactions by promoting the nuclear export of p27, thus facilitating cell cycle progression. Cell.proliferation was negatively regulated when Ser2 of p27 was replaced with Ala. Furthermore, western blot and.immunohistochemical analyses of HCC tissues and their corresponding nontumorous tissues were performed, and we.found that O-GlcNAcylated p27 correlated with cell proliferation in HCC. Together, our results indicate that the dynamic.interplay between O-GlcNAcylation and p27 phosphorylation coordinates and regulates cell proliferation in.hepatocellular carcinoma
