Two-photon imaging of multicellular tumor spheroids A novel method for evaluating the efficacy of CDC25 phosphatase inhibitors

摘要

CDC25 phosphatases are key regulators of the cell cycle. These dual specificity phosphatases activate cyclin-dependent kinase (CDK) complexes by removing inhibitory tyrosine and threonine phos-phorylations on the ATP binding loop. After one final activating phosphorylation by CDK-activating kinase (CAK), CDK/ cyclin complexes are free to initiate progression through the cell cycle. Since CAK phosphorylation is not known to be regulated by cell signaling networks, CDC25s are generally considered to be the main contributors leading to CDK/cyclin activation within the cell. This role also places CDC25s as key components of cell cycle checkpoint pathways. When prompted by DNA damage, ATM and ATR kinases phosphorylate CHK1 and CHK2, which in turn inhibit CDC25s by degradation or relocalization. Without CDC25s available to activate CDK/cyclins, the cell cycle is brought to a halt, allowing the cell to fix the DNA damage or initiate programmed cell death.