TAME

TAME is an inhibitor of anaphase-promoting complex/cyclosome (APC/C or APC), which binds to APC/C and prevents its activation by Cdc20 and Cdh1, produces mitotic arrest. TAME is not cell permeable^[1][2]. IC50 & Target: Anaphase-promoting complex (APC)^[1] In Vitro: The absence of APC substrates, TAME ejects Cdc20 from the APC by promoting Cdc20 auto-ubiquitination in its N-terminal region. Cyclin B1 antagonizes TAME's effect by promoting binding of free Cdc20 to the APC and suppressing Cdc20 auto-ubiquitination^[2].
TAME stabilizes cyclin B1 in Xenopus extract by two mechanisms. First, it reduces the k_cat of the APC^Cdc20/cyclin B1 complex without affecting the K_m, slowing the initial ubiquitination of unmodified cyclin B1. Second, as cyclin B1 becomes ubiquitinated, it loses its ability to promote Cdc20 binding to the APC in the presence of TAME. As a result, cyclin B1 ubiquitination terminates before reaching the threshold necessary for proteolysis^[2].