BEGIN:VCALENDAR VERSION:2.0 PRODID:VideoCast CALSCALE:GREGORIAN METHOD:PUBLISH BEGIN:VEVENT SUMMARY:The Proteasome: Substrate Receptors and Beyond DTSTART:20200221T170000Z DTEND:20200221T180000Z DTSTAMP:20200224T143300Z UID:Videocast--35672 LOCATION:https://videocast.nih.gov/watch=35672 DESCRIPTION:Kylie J. Walters\, Ph.D.\, Acting Chief\, Structural Biophysics Laboratory\, Senior Investigator\, Head\, Protein Processing SectionCenter for Cancer Research\, NCI\, NIH\nNCI’s Center for Cancer Research (CCR) Grand Rounds \n\nResearch in the Walters lab is focused on regulated protein degradation by the proteasome and protein quality control. The proteasome is comprised of a hollow barrel shaped catalytic core particle (CP) where substrate proteolysis occurs and inhibitors used to treat hematological cancers bind. The CP is capped at either end by a >20-subunit regulatory particle (RP) that recognizes\, processes\, and translocates ubiquitinated substrates into the CP for degradation. Dr. Walters’ research is defining mechanistically how the RP interacts with proteasome substrates\, having identified receptor sites for ubiquitinated proteins throughout the RP. By solving 3-dimensional structures of proteasome substrate receptors with ubiquitin chains\, the research group has revealed how each RP receptor recognizes substrates. In addition\, they have identified a dedicated binding site in the RP for ubiquitin E3 ligase E6AP/UBE3A. This site represents the first known binding location at the proteasome for an E3 ligase. In addition to revealing interactions that occur at the proteasome\, Dr. Walters’ group is using atomic resolution structures to develop new strategies for inhibiting ubiquitin-mediated protein degradation. A long-term goal of the Walters group is to develop new therapeutic approaches to target the ubiquitin-proteasome pathway for cancer treatment. For more information about the speaker\, please visit https://ccr.cancer.gov/Structural-Biophysics-Laboratory/kylie-j-walters. X-ALT-DESC;FMTTYPE=text/html:\n\n
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