CHARACTERIZATION OF A UBIQUITIN-INDEPENDENT PATHWAY FOR PROTEASOMAL DEGRADATION - PROJECT SUMMARY/ABSTRACT…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
Assistance award details
- Assistance award identifier
- ASST_NON_R00AG081456_075
- FAIN
- R00AG081456
- Recipient
- THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $249,000
- Period
- Aug 1, 2023 – Jul 31, 2029
- Fiscal year
- 2026
- Place of performance state
- TX
- Source file
- FY2026_All_Assistance_Full_20261006.zip
Description
CHARACTERIZATION OF A UBIQUITIN-INDEPENDENT PATHWAY FOR PROTEASOMAL DEGRADATION - PROJECT SUMMARY/ABSTRACT THE PROTEASOME IS THE MAIN INTRACELLULAR PROTEASE AND IS RESPONSIBLE FOR DEGRADING THOUSANDS OF DIFFERENT PROTEINS. THE MAIN SIGNAL FOR DEGRADATION BY THE PROTEASOME IS THOUGHT TO BE THE POST-TRANSLATIONAL ATTACHMENT OF UBIQUITIN MOLECULES ONTO A SUBSTRATE PROTEIN. WHILE SOME PROTEASOME SUBSTRATES HAVE BEEN REPORTED TO BE TARGETED TO THE PROTEASOME WITHOUT THE USE OF UBIQUITIN, THE EXTENT AND MECHANISM OF UBIQUITIN-INDEPENDENT PROTEASOMAL DEGRADATION REMAIN UNCLEAR. WE HAVE RECENTLY IDENTIFIED HUNDREDS OF PEPTIDES THAT, WHEN FUSED TO THE C-TERMINUS OF ENHANCED GREEN FLUORESCENT PROTEIN (EGFP), ARE DEGRADED BY THE PROTEASOME IN A UBIQUITIN- INDEPENDENT MANNER. HERE, WE PROPOSE TO INVESTIGATE THE MECHANISM OF THIS UBIQUITIN-INDEPENDENT DEGRADATION AND DETERMINE THE ENDOGENOUS SUBSTRATES OF THIS PATHWAY. FIRST, WE WILL DETERMINE IF THE EGFP FUSION SUBSTRATES ARE RECOGNIZED BY THE PROTEASOME DIRECTLY, OR IF THEY ARE SHUTTLED TO THE PROTEASOME BY AN INTERVENING FACTOR (AIM 1). NEXT, WE WILL CHARACTERIZE THE INTERACTION BETWEEN THE RECEPTOR AND SUBSTRATES USING A COMBINATION OF GENETIC AND BIOCHEMICAL METHODS (AIM 2). FINALLY, WE WILL IDENTIFY ENDOGENOUS SUBSTRATES OF THE UBIQUITIN-INDEPENDENT PATHWAY (AIM 3). OVERALL, THESE EXPERIMENTS WILL CHARACTERIZE IN DETAIL THIS NEWLY-UNCOVERED UBIQUITIN-INDEPENDENT PROTEASOME PATHWAY, WHICH MAY HAVE PROFOUND IMPLICATIONS FOR OUR UNDERSTANDING OF THE PROTEASOME AND OF PROTEIN HOMEOSTASIS MORE GENERALLY. I WILL PERFORM THIS RESEARCH AS A POSTDOCTORAL FELLOW UNDER THE MENTORSHIP OF DR. STEPHEN ELLEDGE AT BRIGHAM AND WOMENâS HOSPITAL/HARVARD MEDICAL SCHOOL (HMS) AND INTO MY FUTURE INDEPENDENT RESEARCH CAREER AT A TOP U.S. INSTITUTION. TO ACCOMPLISH MY PROPOSED AIMS, I WILL NEED TO LEARN ESSENTIAL SKILLS IN THE K99 PERIOD FROM DR. ELLEDGE PERTAINING TO ADVANCED GENETIC SCREENING TECHNIQUES. I HAVE ASSEMBLED A TEAM OF COLLABORATO