NIH VideoCast - Regulation of Inflammation by Ubiquitin Modification of Signaling Components

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Regulation of Inflammation by Ubiquitin Modification of Signaling Components

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Air date:	Wednesday, May 21, 2008, 3:00:00 PM Time displayed is Eastern Time, Washington DC Local
Views:	Total views: 309 * This only includes stats from October 2011 and forward.
Category:	WALS - Wednesday Afternoon Lectures
Runtime:	01:09:07
Closed captioning:	Check box to display CC outside of the video Note: You can drag the captioning window around and resize it
Description:	The NIH Director's Wednesday Afternoon Lecture Series: http://www1.od.nih.gov/wals/schedule.htm Proper regulation of inflammation is essential for combating pathogen invasion and maintaining homeostasis. Whereas hypo-responsive hosts succumb to infections, unchecked inflammatory reactions promote a variety of debilitating and fatal conditions including septic shock, autoimmune disease, atherosclerosis, graft rejection, and cancer. Pathogens, host immune cell ligands, and pro-inflammatory cytokines such as Tumor Necrosis Factor-a (TNF-a), Interleukin-1-b (IL1-b), and Lipopolysaccharide (LPS) induce an array of inflammatory responses by activating a variety of cell types. Although much is known about how inflammatory responses are initiated and sustained, less is known about how inflammation is attenuated to maintain a homeostatic balance. The A20 protein is now recognized as a central, negative feedback inhibitor, of NF-kB mediated inflammatory responses. It was originally discovered as an NF-kB inducible gene that was recruited to the assembled proximal signaling complex of pro-inflammatory receptors by virtue of being able to bind to other proximal signaling adaptors including TRAFs and RIP. Analysis revealed seven repeats of a novel type of Cys2/Cys2 zinc finger motif at the carboxy terminus that possessed E3 ligase activity and a amino terminal Ovarian Tumor (OTU) domain that exhibited deubiquitinating activity. Both enzymatic activities were shown to act in concert to attenuate NF-kB signaling from pro-inflammatory receptors. Dixit is profiled in the April 1, 2004, issue of Nature: http://www.nature.com/nature/journal/v428/n6982/full/nj6982-586c.html BIOGRAPHICAL SKETCH: Vishva Dixit, a native of Kenya, East Africa, finished medical school at the top of his class at the University of Nairobi in 1980. Following an year of internship, he pursued further medical training at Washington University School of Medicine in St. Louis, Missouri. As a resident in the Department of Pathology, Vishva was fortunate to be awarded a Josiah Macy fellowship that allowed him to interrupt his residency training and do a postdoctoral fellowship in the Department of Biological Chemistry pursuing the biochemistry of extracellular matrix components. Following completion of residency training in 1986 Vishva joined the Department of Pathology at The University of Michigan as Assistant Professor. He rose through the ranks to be appointed full professor in 1995. During his tenure at Michigan his laboratory worked in many areas including matrix biology and on the characterization of a novel family of receptor protein tyrosine kinases. However, he is best known for his work on apoptosis. His laboratory published a series of groundbreaking papers in the mid nineties in which they defined the molecular components of the death receptor pathway. This importance of this work is reflected in the fact that Vishva was the second most highly cited scientist in all scientific disciplines in 1997. In recognition of these contributions in 1996 he was awarded the Warner-Lambert/Parke-Davis Award in Experimental Pathology. He joined Genentech in 1997 as Director on Molecular Oncology. Under his stewardship the Department has excelled in both basic and translational research and is second to none in the Biotechnology sector. Vishva has published well over a hundred scientific articles and has a significant number of patents to his name. More information available: http://www.gene.com/gene/research/sci-profiles/phychem/dixit/profile.html

NLM Title:	Regulation of inflammation by ubiquitin modification of signaling components / Vishva Dixit.
Author:	Dixit, Vishva. National Institutes of Health (U.S.)
Publisher:
Abstract:	Proper regulation of inflammation is essential for combating pathogen invasion and maintaining homeostasis. Whereas hypo-responsive hosts succumb to infections, unchecked inflammatory reactions promote a variety of debilitating and fatal conditions including septic shock, autoimmune disease, atherosclerosis, graft rejection, and cancer. Pathogens, host immune cell ligands, and pro-inflammatory cytokines such as Tumor Necrosis Factor-a (TNF-a), Interleukin-1-b (IL1-b), and Lipopolysaccharide (LPS) induce an array of inflammatory responses by activating a variety of cell types. Although much is known about how inflammatory responses are initiated and sustained, less is known about how inflammation is attenuated to maintain a homeostatic balance. The A20 protein is now recognized as a central, negative feedback inhibitor, of NF-kB mediated inflammatory responses. It was originally discovered as an NF-kB inducible gene that was recruited to the assembled proximal signaling complex of pro-inflammatory receptors by virtue of being able to bind to other proximal signaling adaptors including TRAFs and RIP. Analysis revealed seven repeats of a novel type of Cys2/Cys2 zinc finger motif at the carboxy terminus that possessed E3 ligase activity and a amino terminal Ovarian Tumor (OTU) domain that exhibited deubiquitinating activity. Both enzymatic activities were shown to act in concert to attenuate NF-kB signaling from pro-inflammatory receptors.
Subjects:	Immunity, Innate--physiology Inflammation--metabolism NF-kappa B--metabolism Signal Transduction--physiology Ubiquitination
Publication Types:	Lecture Webcast
NLM Classification:	QZ 150
NLM ID:	101475730
CIT Live ID:	6224
Permanent link:	https://videocast.nih.gov/watch=6224

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