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Protein kinase, membrane-associated tyrosine- and threonine-specific 1 (PKMYT1) is a membrane-associated kinase of the Wee1 family that negatively regulates cell cycle progression by phosphorylating and inactivating cyclin-dependent kinase 1 (CDK1) at threonine 14 and tyrosine 15. Predominantly localized to the endoplasmic reticulum and Golgi apparatus, PKMYT1 functions in the cytoplasm and is essential for maintaining the G2/M checkpoint, preventing premature mitosis when DNA damage or errors are detected. It is frequently overexpressed in several cancer types, where it supports tumor cell proliferation, migration, and drug resistance, making it a promising therapeutic target for inhibitors in oncology research. PKMYT1 is regulated by polo-like kinase 1 (Plk1) and participates in a feedback loop with Wee1 and Cdc25 phosphatases to tightly control CDK1 activation and cell cycle transitions.
Inhibition of CDK1 activity via phosphorylation at Thr14 and Tyr15, preventing premature mitosis. Checkpoint abrogation: Some drugs promote unscheduled CDK1 activation leading to cell death in cancer cells.
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