<P> In addition, both securin and separase are well - conserved proteins (Figure 1). Note that separase cannot function without initially forming the securin - separase complex . This is because securin helps properly fold separase into the functional conformation . However, yeast does not appear to require securin to form functional separase as anaphase occurs in yeast with a securin deletion mutation . </P> <P> Securin has 5 known phosphorylation sites that are targets of Cdk1; 2 sites at the N - terminal in the Ken - Box and D - box region are known to affect APC recognition and ubiquitination (Figure 2). To initiate the onset of anaphase, securin is dephosphorylated by Cdc14 and other phosphatases . Dephosphorylated securin is recognized by the Anaphase - Promoting Complex (APC) bound primarily to Cdc20 (Cdh1 is also an activating substrate of APC). The APC complex ubiquitinates securin and targets it for degradation by 26S proteasome . This results in free separase that is able to destroy cohesin and initiate chromosome separation . </P> <P> It is thought that securin integrates multiple regulatory inputs to make separase activation switch - like, resulting in sudden, coordinated anaphase . This likely involves a network with several feedback loops, including positive feedback which leads to switch - like behavior . One proposed signaling pathway generating switch - like behavior contains a positive feedback loop for activation of Cdc14 by separase, leading to dephosphorylation and degradation of securin (Figure 3). </P> <P> David Morgan's group found that segregation time of chromosomes 4 and 5 is significantly elongated in budding - yeast strains with mutations in the 2 N - terminal securin phosphorylation sites and securin deletion strains . In addition, these mutant strains exhibited very high rates of mis - segregation compared to normal behavior . Switch - like characteristics are necessary to trigger quick, coordinated chromosomal segregation in anaphase . This means that strong inactivation of separase by securin followed by sudden, rapid destruction of securin and activation of separase is vital for proper anaphase . </P>

Based on the role of securin it must become dephosphorylated just prior to