Air date: Wednesday, December 07, 2011, 3:00:00 PM
Time displayed is Eastern Time, Washington DC Local
Category: Wednesday Afternoon Lectures
Description: O-GlcNAcylation, the cycling of a N-acetylglucosamine monosaccharide on Ser(Thr) residues of nuclear and cytoplasmic proteins, serves as a nutrient/stress sensor to regulate signaling, transcription and cellular metabolism. Recent phospho- and glycomic approaches have shown that an increase in global O-GlcNAcylation affects phospho-site occupancy at nearly every actively cycling site. A chemico-enzymatic photochemical enrichment method, combined with ETD-mass spectrometry allows detection of O-GlcNAc site occupancy at a level of sensitivity comparable to that possible for phosphorylation. These analyses show that crosstalk between site-specific phosphorylation and O-GlcNAcylation is extensive. Many kinases are both modified and regulated by O-GlcNAcylation. The major sensor of cellular energy state, AMPK is O-GlcNAcylated. AMPK and O-GlcNAc transferase share many substrates and the two systems directly interact. Major signaling cascades (eg. CDK1, aurora kinase, polo kinase) that regulate cell division are strikingly affected by a small change in O-GlcNAcylation. O-GlcNAc is part of the histone code, but many of the O-GlcNAc residues are at sites interacting with DNA in the nucleosome, not in the histone tails. Multiple core ribosome proteins are modified by O-GlcNAc, which plays a role in ribosome biogenesis and assembly. O-GlcNAc cycling is strikingly elevated in most forms of cancer. Excessive O-GlcNAcylation of regulatory proteins appears to underlie “glucose toxicity” associated with diabetes. In the brain, reduced O-GlcNAcylation of many proteins is associated with neurodegenerative disease. Thus, O-GlcNAcylation modulates many signaling cascades and phosphate-mediated molecular switches to ÔtuneÕ them to be highly responsive to nutrients and stress.
The NIH Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide.
Author: Dr. Gerald W. Hart, Johns Hopkins University
Permanent link: http://videocast.nih.gov/launch.asp?17013