Uhlmann/Elsevier ! Q V& \( \- E6 c ' [- y$ P/ s$ \% ~1 C# @" H6 LThe separation of sister chromatids at anaphase cannot commence until separase cleaves the cohesin subunit Scc1. Separase is regulated by an inhibitor, securin, that seems to have contradictory characteristics—it prevents Scc1 cleavage by separase, yet at the same time it is required for separase function and correct chromatid separation. Now, Nadine Hornig, Frank Uhlmann (London Research Institute, London), and colleagues explain how securin primes separase for a rapid burst of activity in mitosis.4 z# {& V: i7 z8 n. M+ w
5 @$ Z' B5 e! v6 y& {To promote correct separase function, securin first ensures the nuclear localization of separase. Securin levels normally drop during anaphase and do not increase again until S phase. When the group expressed securin in G1, they found it increased the amount of separase found in the nucleus. But just bringing separase to the nucleus was not enough; securin also acted as a chaperone for separase to achieve the preferred conformation for its protease activity. Separase extracted from cells that contained securin in the previous cell cycle was more active than separase from cells lacking securin. / [5 l! X, H9 O; F, \# Z4 J4 X0 y" j/ g; Z6 j% k
While securin promotes separase activity, it also has two tricks to ensure that the protease does not cleave cohesin until the time is right. "Securin uses a foolproof twofold mechanism," says Uhlmann. "It prevents separase from activating itself and at the same time prevents it from binding to its target substrate." The group found that interaction of separase NH2-terminal and protease domains is crucial for the protease activity. Securin interacted with both domains, disrupting separase self-contact. Securin also prevented separase binding to Scc1. Degradation of securin at anaphase thus suddenly unleashes a high concentration of superactive separase at the right place and right time. 9 M- `7 O. Z: s) d4 w6 v$ d' ?! s* N5 _ 3 ?2 n" T4 V+ z+ xReference: ' p: B5 _* X [0 L2 y ; \; O( R4 w6 gHornig, N., et al. 2002. Curr. Biol. 10.1016/S0969982202008151.(Securin prevents separase from cleaving )作者: 张佳 时间: 2015-5-27 16:17