Chemical biology of mitosis and the ubiquitin-proteasome system.
Building C-2 666A
240 Longwood Avenue
Boston, Massachusetts 02115
Lab Size: Between 5 and 10
Our laboratory studies how ubiquitin‐dependent protein degradation controls cell cycle progression in normal and cancer cells. We integrate biochemical, cell biological, and chemical approaches to study the ubiquitin-proteasome pathway. We are interested in the regulation of the Anaphase‐Promoting Complex (APC), a large multisubunit ubiquitin ligase that targets important mitotic regulators for destruction by the ubiquitin pathway. We are especially interested in the development of new small molecule inhibitors that block APC-dependent degradation, which may be useful for treatment of cancer. Recently, we have also identified small molecules that accelerate proteasomal degradation, which may be useful for treatment of neurodegerative disease. We are also interested in the development of new technologies including novel screening methods and imaging approaches, including long-term time lapse imaging.
F.D. Sigoillot, R.W. King. "Vigilance and validation: Keys to succes in RNAi screening". ACS Chemical Biology 2011, 6:47-60.
X. Zeng, F. Sigoillot, S. Gaur, S. Choi, K.L. Pfaff, D.C. Oh, N. Hathaway, N. Dimova, G.D. Cuny, R.W. King. "Pharmacologic inhibition of the anaphase-promoting complex induces a spindle checkpoint-dependent mitotic arrest in the absence of spindle damage". Cancer Cell 2010, 18: 382-95.
B.H. Lee, M.J. Lee, S. Park, D.C. Oh, S. Elsasser, P.C. Chen, C. Gartner, N. Dimova, J. Hanna, S.P. Gygi, S.M. Wilson, R.W. King, D. Finley. "Enhancement of proteasome activity by a small-molecule inhibitor of USP14". Nature 2010, 467:179-84.
X. Zeng, R.W. King. "An APC/C inhibitor stabilizes cyclin B1 by prematurely terminating ubiquitination." Nature Chem Biol 2012, 8:383-92.
N.V. Dimova, N.A. Hathaway, B.H. Lee, D.S. Kirkpatrick, M.L. Berkowitz, S.P. Gygi, D. Finley, R.W. King. "APC/C-mediated multiple monoubiquitylation provides an alternative degradation signal for cyclin B1." Nature Cell Biol. 2012, 8:383-92.