Kylie J. Walters, Ph.D.
Structural Biophysics Laboratory
Advanced Technology Research Facility (ATRF)/B3330
Frederick, MD 21702
The Walters lab studies the structural and mechanistic basis of ubiquitin signaling events, proteasome function, and protein quality control. We use cell-based assays and a variety of biophysical techniques, our most powerful of which is NMR spectroscopy. This approach has helped to develop a mechanistic understanding of how the proteasome recognizes and processes its substrates. Working with other labs, we have identified Rpn1 and Rpn13 as substrate receptors in the proteasome that bind to ubiquitin chains and the shuttle factors that deliver ubiquitinated substrates to the proteasome. We have found that Rpn13 is targeted in its ubiquitin-binding domain by cell permeable molecules that restrict cancer cell proliferation. This work suggests that Rpn13 is a viable therapeutic target for human cancers. Small molecules that inhibit the catalytic core particle of the proteasome are approved for treatment of hematological cancers. Targeting of Rpn13 is expected to function synergistically with these approved molecules. We continue to study protein-protein interactions in the proteasome and other quality control pathways to understand the determinants of protein targeting for degradation as well as the mechanistic features that go awry in these pathways during carcinogenesis and neurological disorders.
The Protein Processing Section currently has an opening for an outstanding postdoctoral fellow. If you are interested in joining us, please send your C.V. and a statement of interest to firstname.lastname@example.org
Dr. Walters obtained her Ph.D. in Biophysics from Harvard University, where she used NMR spectroscopy to study protein structure and dynamics in Dr. Gerhard Wagner's laboratory. As an American Cancer Society Postdoctoral Fellow with Dr. Peter Howley in the Pathology Department at Harvard Medical School, she studied the ubiquitin signaling pathway. In 2002, Dr. Walters joined the University of Minnesota as an Assistant Professor and was promoted to Associate Professor with tenure in 2008. During this time, her lab used NMR spectroscopy to study ubiquitin signaling for degradation by proteasome. Dr. Walters was an American Cancer Society Research Scholar from 2007-2011. In 2013, she joined the Structural Biophysics Laboratory at the CCR as a Senior Investigator. She was elected as a CCR Women Science Advisor in 2016 and serves on the CCR Science Board.
Lu X, Nowicka U, Sridharan V, Liu F, Randles L, Hymel D, Dyba M, Tarasov SG, Tarasova NI, Zhao XZ, Hamazaki J, Murata S, Burke TR Jr, Walters KJ. Structure of the Rpn13-Rpn2 complex provides insights for Rpn13 and Uch37 as anticancer targets. Nat Commun. 2017;8:15540.
Randles L, Anchoori RK, Roden RB, Walters KJ. The Proteasome Ubiquitin Receptor hRpn13 and Its Interacting Deubiquitinating Enzyme Uch37 Are Required for Proper Cell Cycle Progression. J Biol Chem. 2016;291(16):8773-83.
Shi Y, Chen X, Elsasser S, Stocks BB, Tian G, Lee BH, Shi Y, Zhang N, de Poot SA, Tuebing F, Sun S, Vannoy J, Tarasov SG, Engen JR, Finley D, Walters KJ. Rpn1 provides adjacent receptor sites for substrate binding and deubiquitination by the proteasome. Science. 2016;351(6275).
He F, Wollscheid HP, Nowicka U, Biancospino M, Valentini E, Ehlinger A, Acconcia F, Magistrati E, Polo S, Walters KJ. Myosin VI Contains a Compact Structural Motif that Binds to Ubiquitin Chains. Cell Rep. 2016;14(11):2683-94.
Chen X, Lee BH, Finley D, Walters KJ. Structure of proteasome ubiquitin receptor hRpn13 and its activation by the scaffolding protein hRpn2. Mol Cell. 2010;38(3):404-15.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
This page was last updated on June 15th, 2017