checkpoints of G1/S and G2/M as well as Cdc25B and Cdc25C which both control the G2/M checkpoint. Mitosis Myt 1 and Wee 1 kinases work together to inhibit Cdk 1 before mitosis. Myt 1 and Wee 1 concentrations are high throughout most of the cell cycle to ensure the inactivation of Cdk 1. During mitosis, concentrations of Myt 1 and Wee 1 decrease substantially which allows for the dephosphorylation activity of phosphatases in the Cdc 25 family and the subsequent activation of Cdk 1. Subcellular distribution Myt 1 is located in the membranes of the Golgi apparatus and the Endoplasmic reticulum. Since almost all cyclin B1-Cdk 1 complexes are found in the cytoplasm, Myt 1 may be the most important inhibitory kinase for Cdk 1. Since Wee 1 is mostly located in the nucleus, it is believed that Wee 1 maintains the inhibition of the small amount of Cdk 1 that is found in the nucleus while Myt 1 does the rest of the inhibition. Various studies on the deletion of the Wee 1 gene in Drosophila show that an absent Wee 1 is not lethal. This suggests that the inhibition of Cdk 1 caused by Myt 1 is sufficient for mitosis. Further evidence that Myt 1 is the primary inhibitor of Cdk 1 is that Wee 1 is not found in Xenopus oocytes, leaving Myt 1 to be the sole inhibitor of Cdk 1. Regulation The regulation of Myt 1, Wee 1, and Cdc25 lies in a positive feedback loop with Cdk 1. To regulate these three proteins, Cdk 1 hyperphosphorylates the N-terminal regulatory regions. This hyperphosphorylation activates Cdc25 and inhibits Myt 1 and Wee 1. The activation of Cdc25 causes an increase in its levels and the inhibition of Myt 1 and Wee 1 causes a decrease in their levels. This positive feedback led by Cdk 1 creates a bistable system where the cell has both a state of stable inactivity of Cdk 1 and a state of stable Cdk 1 activity. This regulatory system creates a switch where Cdk 1 can be turned on and off quickly and ensures that the process will still operate even if some part fails. Protein kinases AKT1/PKB and PLK (Polo-like kinase) have also been shown to phosphorylate and regulate the activity of Myt 1. Alternatively spliced transcript variants encoding distinct isoforms have been reported. References Further reading External links EC 2.7.11