Abstract:
:O-linked N-acetylglucosamine ( O-GlcNAc) is a ubiquitous post-translational modification of proteins and is essential for cell function. Quantifying the dynamics of O-GlcNAcylation in a proteome-wide level is critical for uncovering cellular mechanisms and functional roles of O-GlcNAcylation in cells. Here, we develop an isotope-coded photocleavable probe for profiling protein O-GlcNAcylation dynamics using quantitative mass spectrometry-based proteomics. This probe enables selective tagging and isotopic labeling of O-GlcNAcylated proteins in one step from complex cellular mixtures. We demonstrate the application of the probe to quantitatively profile O-GlcNAcylation sites in 293T cells upon chemical induction of O-GlcNAc levels. We further applied the probe to quantitatively analyze the stoichiometry of O-GlcNAcylation between sorafenib-sensitive and sorafenib-resistant liver cancer cells, which lays the foundation for mechanistic investigation of O-GlcNAcylation in regulating cancer chemoresistance. Thus, this probe provides a powerful tool to profile O-GlcNAcylation dynamics in cells.
journal_name
ACS Chem Bioljournal_title
ACS chemical biologyauthors
Li J,Li Z,Duan X,Qin K,Dang L,Sun S,Cai L,Hsieh-Wilson LC,Wu L,Yi Wdoi
10.1021/acschembio.8b01052subject
Has Abstractpub_date
2019-01-18 00:00:00pages
4-10issue
1eissn
1554-8929issn
1554-8937journal_volume
14pub_type
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