Securin is a protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 involved in control of the metaphase-anaphase transition and anaphase onset. Following bi-orientation of chromosome

Chromosome

A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...

 pairs and inactivation of the spindle checkpoint system, the underlying regulatory system, which includes securin, produces an abrupt stimulus that induces highly synchronous chromosome separation in anaphase

Anaphase

Anaphase, from the ancient Greek ἀνά and φάσις , is the stage of mitosis or meiosis when chromosomes move to opposite poles of the cell....

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Securin and Separase

Securin is initially present in the cytoplasm and binds to separase

Separase

Separase is a cysteine protease responsible for triggering anaphase by hydrolysing cohesin which is the protein responsible for binding sister chromatids during metaphase. In humans, separase is encoded by the ESPL1 gene.- Discovery :...

, a protease

Protease

A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....

 that degrades the cohesin rings that link the two sister chromatids. Separase is vital for onset of anaphase. This securin-separase complex is maintained when securin is phosphorylated by , inhibiting ubiquitination. When bound to securin, separase is not functional.

In addition, both securin and separase are well-conserved proteins (Figure 1). Interestingly, 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.

Basic mechanism

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

Cdc14

Cdc14 was defined by Hartwell in his famous screen for loci that control the cell cycle of Saccharomyces cerevisiae. Cdc14 was later shown to encode a protein phosphatase. Cdc14 is dual-specificity, which means it has serine/threonine and tyrosine-directed activity. A preference for serines...

 and other phosphatases. Dephosphorylated securin is recognized by the Anaphase-Promoting Complex (APC) bound primarily to Cdc20

CDC20

The cell-division cycle protein 20 is an essential regulator of cell division that is encoded by the CDC20 gene in humans. To the best of current knowledge its most important function is to activate the anaphase promoting complex , a large 11-13 subunit complex that initiates chromatid separation...

(Cdh1 is also an activating substrate of APC). The APC^Cdc20 complex ubiquitinates securin and targets it for degradation. This results in free separase that is able to destroy cohesion and initiate chromosome separation.

Network characteristics

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).

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.

Overall, securin and separase act in an anaphase-regulating network. Figure 4 depicts a potential network diagram.