Sci. STKE, 5 October 2004
CELL CYCLE Inhibiting Cell Cycle Progression and the Proteasome
The proteasome degrades ubiquitin-tagged proteins in the cytosol. Verma et al. (see the Perspective by Bellows and Tyers) performed a chemical genetic screen in Xenopus extracts to identify small-molecule inhibitors of cell-cycle progression. One class of inhibitors, the ubistatins, inhibited cyclin B degradation and thereby cell-cycle progression. Ubistatins also prevented the interaction of ubiquitinated substrates with purified proteasomes. Ubistatins target the same ubiquitin interface recognized by known, therapeutically important ubiquitin-binding proteins.
R. Verma, N. R. Peters, M. D'Onofrio, G. P. Tochtrop, K. M. Sakamoto, R. Varadan, M. Zhang, P. Coffino, D. Fushman, R. J. Deshaies, R. W. King, Ubistatins inhibit proteasome-dependent degradation by binding the ubiquitin chain. Science 306, 117-120 (2004). [Abstract] [Full Text]
Citation: Inhibiting Cell Cycle Progression and the Proteasome. Sci. STKE 2004, tw353 (2004).
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