Function of cyclin E-Cdk2 substrate NPAT
We have been interested in understanding the mechanisms of the G1-to-S phase transition in mammalian cells. One of the critical regulators of the G1/S phase transition is the cyclin-dependent kinase cyclin E-Cdk2 complex. We have identified a physiological downstream target of cyclin E-Cdk2, NPAT, and characterized its functions in cell cycle progression. We have found that NPAT plays a crucial role in coordinating transcriptional activation of all histone subtypes during the G1-to-S phase transition as well as initiation of DNA replication, suggesting that NPAT provides a critical link between cell cycle machinery and these two major S phase events and couples histone gene expression and DNA replication upon S phase entry. More recently, we have discovered that NPAT regulates cellular process in addition to cell cycle progression. These observations indicate that NPAT plays a key role in multiple cellular processes and in their coordination, which are required for maintaining genetic stability. Thus, understanding the functions and regulation of NPAT may provide new insights not only into mechanism of cellular proliferation but also into the mechanism of tumor formation. We are investigating the molecular mechanisms by which NPAT executes its multiple functions in mammalian cells.
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