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Microgenetics: What We Can Learn About Protein Degradation from Bits of Genes

The Cancer Biology Lecture

Event Details

Friday Lecture Series
Stephen Elledge, Ph.D., Gregor Mendel Professor of Genetics and of Medicine, Harvard Medical School; investigator, Howard Hughes Medical Institute

Degrons are minimal elements that mediate the interaction of proteins with degradation machineries to promote proteolysis. Despite their central role in proteostasis, the number of known degrons remains small and a facile technology to characterize them is lacking. Using a strategy combining Global Protein Stability (GPS) profiling with a synthetic human peptidome, Dr. Elledge identifies thousands of peptides containing degron activity. Using CRISPR screening, Dr. Elledge and his lab established that the stability of many proteins is regulated through degrons located at their C-terminus. They characterize eight Cullin-RING E3 ubiquitin ligase (CRL) complexes adaptors that regulate C-terminal degrons, including six CRL2 and two CRL4 complexes, and computationally implicate multiple non-CRLs in end recognition. Human proteome analysis revealed that the C-termini of eukaryotic proteins are depleted for C-terminal degrons, suggesting an E3 ligase-dependent modulation of proteome composition. They propose that a series of ‘C-end rules’ operate to govern protein stability and shape the eukaryotic proteome. Using the GPS-peptidome strategy, Dr. Elledge has uncovered many distinct classes of degrons with interesting properties as well as stabilons which appear to prevent the degradation of proteins.

Dr. Elledge's research interests focus on using genetics and genetic technologies to solve problems relevant to human disease. He has made fundamental contributions to the current understanding of the cellular mechanisms of cancer and the development of novel therapeutic strategies. More recently, he and his team developed immunological tools, such as VirScan, that allow researchers to test for current and past viral infections using a single drop of blood.

He is a member of the National Academy of Sciences, the National Academy of Medicine, and the American Academy of Arts and Sciences. Dr. Elledge has been the recipient of many awards including the 2010 Dickson Prize, the 2013 Lewis S. Rosenstiel Award for Distinguished Work in the Basic Medical Sciences, the 2013 Canada Gairdner International Award, the 2015 Albert Lasker Basic Medical Research Award, and the 2017 Breakthrough Prize in Life Sciences.

Justin Sloboda
(212) 327-7785
Open to
James Darnell, M.D.
Refreshments, 3:15 p.m. - 3:45 p.m., Abby Lounge
Justin Sloboda
(212) 327-7785

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