Abstract: Method for identifying compounds that interfere with or modulate sister chromatid separation in animal or plant cells by modulating a protease with separin-like cysteine endopeptidase activity. Inhibitors of separin activity are useful in cancer therapy, to prevent birth defects and to increase ploidy in plants.

Abstract: A screening method for identifying specific APC inhibitors comprises a primary screen in which a compound is tested for its ability to interfere with binding of CDH1 or CDC20 to the APC and a secondary screen, in which the compound is tested for its ability to interfere with the activation of the APC by CDH1 or CDC20.

Abstract: Screening methods for identifying separase inhibitors based on active forms of separase and compounds identified in such methods.

Abstract: Screening methods for identifying compounds that inhibit the ubiquitination reaction mediated by the APC are based on the ability of the APC subunit APC11 to form multiubiquitin chains. A compound's ability to interfere with self-ubiquitination of APC11, with the formation of multiubiquitin chains independent of their attachment to APC11 or with ubiquitination of an APC substrate can be measured.

Abstract: The present invention provides a systematic and practical approach for the identification of candidate agents able to inhibit ubiquitin-mediated degradation of a cell-cycle regulatory protein, such as cyclins. One aspect of the present invention relates to a method for identifying an inhibitor of ubiquitin-mediated proteolysis of a cell-cycle regulatory protein by (i) providing a ubiquitin-conjugating system that includes the regulatory protein and ubiquitin under conditions which promote the ubiquitination of the target protein, and (ii) measuring the level of ubiquitination of the subject protein brought about by the system in the presence and absence of a candidate agent. A decrease in the level of ubiquitin conjugation is indicative of an inhibitory activity for the candidate agent.