Title : Modification of
p27 with
O-linked N-acetylglucosamine regulates cell proliferation in hepatocellular carcinoma
Abstract :
- 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 identified 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 modification 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
- © 2016 Wiley Periodicals, Inc