Dynamic Crosstalk between GlcNAcylation and Phosphorylation: Roles in Signaling, Transcription and Human Disease

Author(s): Shino Shimoji, Kyoungsook Park, Gerald W. Hart.

Journal Name: Current Signal Transduction Therapy

Volume 5 , Issue 1 , 2010

Become EABM
Become Reviewer

Abstract:

GlcNAcylation is a dynamic cytoplasmic and nuclear post-translational sugar modification of serine/threonine residues. The addition and removal of O-GlcNAc are regulated by O-GlcNAc Transferase and O-GlcNAcase, respectively. Over ∼1000 proteins have been identified to be GlcNAcylated with over 240 mapped sites. O-GlcNAc is involved in critical cellular functions, such as cell-cycle regulation, apoptosis, stress responses, signaling, transcription, and translation. O-GlcNAc also plays pivotal roles in diseases, such as diabetes, neurodegenerative disease and cancer, and immunological regulation, such as T-cell activation. Through comparative proteomic analysis of resting and activated T-cells, we identified potentially GlcNAcylated proteins involved in post-signaling events of T-cell activation. O-GlcNAc on 58 proteins involved in processes, such as DNA replication, cytoskeletal rearrangement, chromatin remodeling, and RNA processing, were altered by T-cell activation. GlcNAcylation and phosphorylation are similar in abundance and cellular/ biological function, and their regulation is deeply intertwined. The two modifications regulate each other at the sitelevel by reciprocally influencing site-occupancy, and at the enzymatic-activity level by each modification modulating the catalytic activity of the enzymes involved in the other modification. This paper will focus on recent developments in the interplay between O-GlcNAc and phosphorylation, and O-GlcNAcs roles in human disease and immunology.

Keywords: O-GlcNAc, GlcNAcylation, phosphorylation, crosstalk, disease, lymphocyte

Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 5
ISSUE: 1
Year: 2010
Page: [25 - 40]
Pages: 16
DOI: 10.2174/157436210790226528

Article Metrics

PDF: 10