title: Hyper-O-GlcNAcylation of YB-1 affects Ser102 phosphorylation and promotes cell proliferation in hepatocellular carcinoma.
abstract: As an essential post-translational modification, O-GlcNAcylation has been thought to be able to modulate various nuclear and cytoplasmic proteins and is emerging as a key regulator of multiple biological processes, such as transcription, cell growth, signal transduction, and cell motility. Recently, authoritative glycomics analyses have reported extensive crosstalk between O-GlcNAcylation and phosphorylation, which always dynamically interplay with each other and regulate signaling, transcription, and other cellular processes. Also, plentiful studies have shown close correlation between YB-1 phosphorylation and tumorigenesis. Therefore, our study aimed to determine whether YB-1 was O-GlcNAc modified and whether such modification could interact with its phosphorylation during the process of HCC development. Western blot and immunohistochemistry were firstly conducted to reveal obvious up-regulation of YB-1, OGT and O-GlcNAc modification in HCC tissues. What is more, not only YB-1 was identified to be O-GlcNAcylated but hyper-O-GlcNAcylation was demonstrated to facilitate HCC cell proliferation in a YB-1 dependent manner. Moreover, we detected four specific O-GlcNAc sites and confirmed T126A to be the most effective mutant in HCC cell proliferation via close O-GlcNAcylation-phosphorylation interaction. Even more interestingly, we discovered that T126A-induced HCC cell retardation and subdued transcriptional activity of YB-1 could be partially reversed by T126A/S102E mutant. From all above, it is not difficult to find that glycosylated-YB-1 mainly enhanced cell proliferation through congenerous actions with YB-1 phosphorylation and thus played indispensable roles in fine-tuning cell proliferation and procession of HCC.
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, People's Republic of China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qi-xiu Road, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qi-xiu Road, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
authors.affiliation: Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Runzhou
authors.initials: R
authors.lastname: Ni
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, People's Republic of China. Electronic address: lch1516@yeah.net.
authors.forename: Cuihua
authors.initials: C
authors.lastname: Lu
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qi-xiu Road, Nantong 226001, Jiangsu Province, People's Republic of China; Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, Jiangsu Province, People's Republic of China. Electronic address: shag@ntu.edu.cn.
authors.forename: Aiguo
authors.initials: A
authors.lastname: Shen
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D012694:Serine / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D051840:Y-Box-Binding Protein 1 / Q000378:metabolism*
chemical_list: D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D012694:Serine; D000117:Acetylglucosamine
keywords: Cell proliferation; Hepatocellular carcinoma; O-GlcNAc; Ser102 phosphorylation; YB-1