Wee1Myt1

Wee1Myt1 refers to the Wee1-like and Myt1-like kinases, a small family of conserved serine/threonine kinases that inhibit CDK1/cyclin B by phosphorylating it at inhibitory sites such as Tyr15 (and, in some contexts, Thr14). They are key regulators of the G2/M checkpoint, preventing premature entry into mitosis in response to DNA damage or incomplete replication.

In vertebrates, two distinct kinases, Wee1 and Myt1, perform this regulatory function. Wee1 is primarily nuclear and cytoplasmic, while Myt1 associates with the Golgi and other endomembrane compartments; both possess a conserved kinase domain and regulatory regions that modulate activity and localization. They can have overlapping roles, providing redundancy to ensure proper control of mitotic entry. Loss or reduction of Wee1 activity often leads to premature mitosis and genomic instability, whereas loss of Myt1 alone can yield milder phenotypes; combined loss typically produces more severe defects.

Evolutionarily, Wee1 and Myt1 have conserved functions across eukaryotes. In yeast, homologous kinases such as Swe1 (and Mik1 in some species) fulfill similar roles in delaying mitosis through CDK1 inhibition, illustrating the depth of this checkpoint mechanism.

Clinical significance centers on cancer therapy. Wee1 inhibitors, such as adavosertib (AZD1775), are being explored to sensitize tumor cells to DNA-damaging treatments by abrogating the G2/M checkpoint, particularly in p53-deficient cancers. Myt1-related targeting is less developed but is an area of ongoing investigation. The Wee1/Myt1 family remains a focus for understanding cell cycle control and developing therapeutic strategies that exploit replication stress in cancer.