447회 Functional roles of O-GlcNAc modification on nucleocytoplasmic pr…

447회 

연사:  조진원 박사

제목 : Functional roles of O-GlcNAc modification on nucleocytoplasmic proteins

Abstract 

O-GlcNAc modification is a new form of nucleocytoplasmic protein glycosylation found in all eukaryotes. Like phosphorylation, this modification is ubiquitous and very dynamic. The O-GlcNAc is modified at serine and threonine residues of the targeted proteins and its dynamic modification is caused by the action of O-GlcNAc transferase (OGT) and O-GlcNAcase. Because O-GlcNAc modification sites are shared with phosphorylation, this modification appears to have a ‘yin-yang’ relationship with phosphorylation with many regulatory proteins and to play an important role in regulation of protein function. More than 100 proteins have been identified as O-GlcNAc modified proteins and these proteins can be categorized into mainly three groups; nuclear proteins (ex. many transcription factors, chromatin proteins, oncogene proteins, etc), cytoskeletal proteins (ex. cytokeratins, MAPs, tau, etc) and other proteins (ex. β-amyloid precursor proteins, heat shock proteins, etc). Main focus in my lab is to identify more O-GlcNAcylated glycoproteins related to cellular function and to elucidate the function of this modification and its attachment sites. Recently we found function and attachment sites of O-GlcNAc modification in p53 and NF-kB. In the case of p53, O-GlcNAc modification increases life span of p53 as O-GlcNAcylated p53can evade from ubiquitination and proteolysis via proteasome. Its attachment site was identified using quadrupole time-of flight tandem mass spectrometry (Q-TOF MS) and it turned out that the site was shared with phosphorylation by COP9 signalosome. In the case of NF-kB, O-GlcNAc modification caused to detach fromI-kB without any signal, and O-GlcNAcylated NF-kB stayed inside nucleus longer and showed more transcriptional activation. More O-GlcNAcylated NF-kB existed in various organs from diabetic mouse, and this may indicate that O-GlcNAcylated NF-kB would be an important factor to cause complexion of diabetes. Research of O-GlcNAc modification is rapidly growing field and especially O-GlcNAc modification is very important in diabetes, neural disease and development, and many cancer.

KEYWORDS: O-GlcNAc, diabetes, p53, NF-kB