earticle

영어

O-linked beta-N-acetylglucosamine (O-GlcNAc) modification is one of the post-translational modifications. Protein O-GlcNAcylation is reversibly regulated by O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT). More than 800 proteins as diverse as transcription factors, enzymes, cytoskeletal proteins, ribosomal proteins and chaperones have been identified to be modified with O-GlcNAc. Thus, protein O-GlcNAcylation appears to be involved in many different cellular activities regulating in transcription, translation, protein degradation, protein localization and protein-protein interaction. Moreover, O-GlcNAc modification has important and global effects on various cellular signal pathways because of the reciprocal relationship between O-GlcNAc and O-phosphate. Recently, O-GlcNAc modification, as a sensor of cellular states, has been implicated in human diseases including diabetes, neurodegenerative diseases and cancer. We found that O-GlcNAcylation pattern is changed during all-trans retinoic acid (tRA)-induced neutrite outgrowth in the MN9D cell line. We identified several O-GlcNAcylated proteins including alpha- and beta-tubulin and detected O-GlcNAc modified regions between residues 173 and 185 of tubulin and between residues 216 and 238 of beta-tubulin by using mass spectrometry. Also, We found that overexpressing OGT or introducing OGA inhibitor such as NButGT, PUGNAc, increases O-GlcNAcylation on alpha-tubulin, which ultimately leads to inhibition of tubulin polymerization. Accordingly, Our data indicate that the O-GlcNAcylation of tubulin negatively regulates microtubule formation