Editors' ChoiceCell Cycle

Inhibiting Cell Cycle Progression and the Proteasome

Science's STKE  05 Oct 2004:
Vol. 2004, Issue 253, pp. tw353
DOI: 10.1126/stke.2532004tw353

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]

D. S. Bellows, M. Tyers, Chemical genetics hits "reality." Science 306, 67-68 (2004). [Summary] [Full Text]