Event Detail (Archived)
How a Ubiquitin-like Protein Brings Ubiquitylation to Life
The William H. Stein Memorial Lecture
- Friday Lecture Series
Brenda Schulman, Ph.D., director and scientific member, Max Planck Institute of Biochemistry
A predominant form of eukaryotic regulation involves post-translational modification by ubiquitin and ubiquitin-like proteins. Much of this regulation is mediated by the large family of cullin-RING E3 ubiquitin ligases (CRLs). CRLs direct ≈20% of all proteasome-dependent degradation, regulate virtually all eukaryotic processes, and serve as one of the hottest drug discovery platforms in pharma and biotech. The more than 250 human CRL family members regulate processes including the immune response, transcription, signal transduction, cell division, cell death, development, and numerous facets of neurobiology. Moreover, many CRLs are mutated in diseases, including cancers, heart diseases, and developmental disorders. A variety of CRLs are usurped by HIV to suppress immunity and promote infectivity. And due to revolutionary cancer treatments modulating CRL targeting, CRLs are the focus of a billion-dollar drug discovery industry aimed at eliciting ubiquitylation of disease-causing proteins.
Numerous facets of CRL activation – from E3 ligase assembly to catalysis of ubiquitylation to subsequent processing of ubiquitylated substrates – depend on the dynamic linkage and removal of the distinctive UBL NEDD8. NEDD8 is nearly 60% identical to ubiquitin, yet it predominantly regulates CRLs. In her talk, Dr. Schulman will describe her lab's findings that reveal the marvelous ways NEDD8 uniquely brings CRLs – and a large fraction of all ubiquitylation - to life.
Dr. Schulman’s lab is recognized for illuminating mechanisms of ubiquitin and ubiquitin-like protein ligation, and for using a distinctive biochemical reconstitution approach to identify novel in vivo regulatory pathways. Schulman received her Ph.D. from M.I.T. and did postdoctoral training at MGH Cancer Center and Memorial Sloan-Kettering Cancer Center. She started her lab at St. Jude Children’s Research Hospital in 2001, where she was an Investigator of the Howard Hughes Medical Institute, and the Joseph Simone Chair in Basic Research, and retains an adjunct faculty position. Schulman became a full-time Director and Scientific Member at the Max Planck Institute of Biochemistry in 2017. Schulman was elected to the American Academy of Arts and Sciences in 2012, the National Academy of Sciences in 2014, EMBO in 2018, the German Academy Leopoldina in 2019, and recently received the 2019 Gottfried Wilhelm Leibniz Prize and Ernst Jung Prize for Medicine.
- Open to
- Hermann Steller
- Refreshments, 3:15 p.m. - 3:45 p.m., Abby Lounge
- Justin Sloboda
- (212) 327-7785