TAME (Tosyl-Arginine Methyl Este), an inhibitor of the late-promoting complex (APC/C or APC), inhibits APC-dependent protein hydrolysis by competing for APC binding with the C-terminal isoleucine-arginine tail of the APC activator cytokinesis cycle 20 (Cdc20). TAME binds to and prevents APC binding by Cdc20 and Cdh20. TAME binds to APC and prevents its activation by Cdc20 and Cdh1.

APC:12 µM.

In the absence of an APC substrate, TAME repels Cdc20 from APC by inducing its auto-ubiquitination in its N-terminal region, while Cyclin B1 counteracts the effect of TAME by promoting the binding of free Cdc20 to APC and inhibiting the auto-ubiquitination of Cdc20.
TAME stabilized Cyclin B1 in African Xenopus extracts by two mechanisms. First, TAME reduced the kcat value of the APC^Cdc20/cyclin B1 complex without affecting the Km value, thereby slowing down the initial ubiquitination process of unmodified Cyclin B1. Second, as Cyclin B1 is progressively ubiquitinated, it gradually loses its ability to promote Cdc20 binding to APC in the presence of TAME. As a result, the ubiquitination of Cyclin B1 is terminated before reaching the threshold at which protein hydrolysis is required. [2]