期刊
EXPERIMENTAL CELL RESEARCH
卷 314, 期 15, 页码 2774-2787出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2008.05.017
关键词
beta-catenin; O-GlcNAcylation; nuclear localization; transcriptional activity; oncogenic properties
beta-catenin plays a role in intracellular adhesion and regulating gene expression. The latter role is associated with its oncogenic properties. Phosphorylation of beta-catenin controls its intracellular expression but mechanism/s that regulates the nuclear localization of beta-catenin is unknown. We demonstrate that 0-GlcNAc glycosylation (O-GlcNAcylation) of beta-catenin negatively regulates its levels in the nucleus. We show that normal prostate cells (PNTIA) have significantly higher amounts of O-GIcNAcylated beta-catenin compared to prostate cancer (CaP) cells. The total nuclear levels of beta-catenin are higher in the CaP cells than PNTIA but only a minimal fraction of the nuclear beta-catenin in the CaP cells are O-GlcNAcylated. increasing the levels of O-GlcNAcylated beta-catenin in the CaP cells with PUGNAc (O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) amino-N-phenylcarbamate) treatment is associated with a progressive decrease in the levels of beta-catenin in the nucleus. TOPFlash reporter assay and mRNA expressions of beta-catenin's target genes indicate that O-GlcNAcylation of beta-catenin results in a decrease in its transcriptional activity. We define a novel modification of beta-catenin that regulates its nuclear localization and transcriptional function. @ 2008 Elsevier Inc. All rights reserved.
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