The protein Myt1 is a regulatory component in the body. It is a protein kinase, an enzyme that modifies other proteins by adding phosphate groups. This action acts as a safety measure to ensure cellular processes proceed correctly. Myt1’s primary role is to act as a brake, halting a cell’s progression through its life cycle to ensure everything is in order before it divides.
Myt1’s Function in Cell Division
The cell cycle is a sequence of events divided into four main phases: G1, S, G2, and M. During the G1 and S phases, the cell grows and replicates its DNA, while the G2 phase is a final preparation stage before mitosis (M phase), where it divides into two daughter cells. The transition from G2 to M is controlled by a checkpoint system to ensure the cell is prepared.
Myt1 is a key protein at this G2/M checkpoint. Its responsibility is to prevent cells from entering mitosis prematurely, particularly if their DNA is damaged or not fully replicated. It does this by targeting Cyclin-Dependent Kinase 1 (Cdk1), the protein that drives the cell into mitosis. Myt1 adds an inhibitory phosphate group to specific sites on Cdk1, namely threonine-14 and tyrosine-15.
This phosphorylation acts like a switch, turning Cdk1 off. By inactivating Cdk1, Myt1 pauses the cell cycle in the G2 phase. This pause gives the cell time to complete DNA replication or repair any damage. Once the cell’s internal systems give an “all-clear” signal, another enzyme removes these inhibitory phosphates, allowing Cdk1 to activate and push the cell into mitosis.
The Myt1 and Wee1 Partnership
Myt1 collaborates with a partner protein, Wee1, to enforce the G2/M checkpoint. Both Myt1 and Wee1 are kinases that inhibit Cdk1 through phosphorylation to prevent premature entry into mitosis. This redundancy provides a robust safety mechanism, ensuring the “stop” signal is reliable.
The main distinction between these proteins is their location within the cell. Wee1 functions inside the cell’s nucleus, while Myt1 is anchored to membranes in the cytoplasm, such as the endoplasmic reticulum and Golgi apparatus. This spatial separation means Cdk1 is kept in check in multiple cellular locations.
As Cdk1 moves between the cytoplasm and the nucleus, it encounters these inhibitors. Myt1 can also sequester Cdk1 in the cytoplasm, further restricting its access to the nucleus and preventing it from initiating mitosis. This partnership ensures Cdk1 activity is controlled until the cell is ready to divide.
Consequences of Myt1 Dysregulation
Precise regulation of the cell cycle by proteins like Myt1 is necessary for health. When this system is disrupted, the consequences can be severe. If Myt1 function is altered, the “brake” on cell division weakens, permitting cells to bypass the G2/M checkpoint and enter mitosis prematurely.
This premature entry into mitosis is dangerous. If a cell divides before its DNA has been fully and accurately copied, or if it proceeds with damaged DNA, the resulting daughter cells will inherit an incomplete or corrupted set of genetic instructions. This leads to genetic instability, where the chance of mutations and chromosomal abnormalities increases with each division.
Genetic instability is a hallmark of cancer. The accumulation of genetic errors can lead to the activation of genes that promote uncontrolled growth and the inactivation of genes that would normally suppress tumor formation. Therefore, Myt1’s failure to regulate the G2/M checkpoint can contribute to the development and progression of cancer. Overexpression of the gene that produces Myt1, PKMYT1, has been linked to worse outcomes in several cancers, including lung and liver cancer.
Myt1 as a Therapeutic Target
While Myt1’s normal function helps prevent cancer, researchers are exploring an interesting strategy: inhibiting Myt1 to treat existing cancers. Many cancer cells are under stress from rapid, error-prone division. They often have faulty DNA and become dependent on checkpoints, like the one controlled by Myt1 and Wee1, to pause and repair damage to survive.
This dependency creates a vulnerability that can be exploited. Scientists are developing drugs, known as Myt1 inhibitors, that block the protein’s activity. One such inhibitor, lunresertib, has shown promise in selectively killing tumor cells.
By inhibiting Myt1, these drugs push unstable cancer cells past a critical point. Forced to enter mitosis with extensive DNA damage, the cancer cells undergo a form of cellular suicide called mitotic catastrophe. Healthy cells, which are not under the same replicative stress and have other functional checkpoints, are less affected by this approach. This makes Myt1 an attractive target for therapies that can selectively eliminate cancer cells while sparing normal tissue.