DF/HCC Program Affiliation

Breast Cancer
Cancer Cell Biology

Research Abstract

Our laboratory studies how ubiquitin-dependent protein degradation controls cell cycle progression in normal and cancer cells. We are interested in the regulation of the Anaphase-Promoting Complex, a large multisubunit complex that targets many important mitotic regulators for destruction by the ubiquitin pathway. To study this problem, we apply biochemical reconstitution with small molecule inhibitors to dissect mechanism of action. We are also interested in how chromosome segregation is perturbed in cancer cells, and we employ long-term time lapse imaging to understand how normal cells and cancer cells cope with defects in chromosome segregation. We are also using siRNA screening approaches to identify genes that modulate the sensitivity of breast cancer cells to trastuzumab (herceptin).

Publications

• Kirkpatrick DS, Hathaway NA, Hanna J, Elsasser S, Rush J, Finley D, King RW, Gygi SP.Quantitative analysis of in vitro ubiquitinated cyclin B1 reveals complex chain topology.Nat Cell Biol 2006 Jul;8(7):700-10.
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• Shi Q, King RW.Chromosome nondisjunction yields tetraploid rather than aneuploid cells in human cell lines.Nature 2005 Oct 13;437(7061):1038-42.
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• Verma R, Peters NR, D'Onofrio M, Tochtrop GP, Sakamoto KM, Varadan R, Zhang M, Coffino P, Fushman D, Deshaies RJ, King RW.Ubistatins inhibit proteasome-dependent degradation by binding the ubiquitin chain.Science 2004 Oct 1;306(5693):117-20.
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