Cyclin-Dependent Kinase 2 (CDK2) is a crucial enzyme in the regulation of the cell cycle. It belongs to the family of serine/threonine protein kinases and is encoded by the CDK2 gene in humans . CDK2 plays a pivotal role in the transition from the G1 phase to the S phase of the cell cycle, where cells prepare for DNA replication and mitosis . The recombinant form of CDK2, expressed in Sf9 insect cells, is widely used in research to study its function and regulation.
CDK2 is a catalytic subunit of the cyclin-dependent kinase complex. Its activity is tightly regulated by its association with cyclins, particularly cyclin E and cyclin A . Cyclin E binds to CDK2 during the G1 phase, facilitating the transition to the S phase, while cyclin A is involved in the progression through the S phase . The kinase activity of CDK2 is also regulated by phosphorylation at specific residues, which modulates its activity and stability .
The recombinant form of CDK2 is typically produced using the baculovirus expression system in Sf9 insect cells. This system allows for high-level expression of recombinant proteins with post-translational modifications similar to those in mammalian cells. The process involves the following steps:
CDK2 is essential for the regulation of the cell cycle. It phosphorylates various substrates, including the retinoblastoma protein (Rb), which is crucial for the G1/S transition . The phosphorylation of Rb by CDK2/Cyclin E complex leads to the release of E2F transcription factors, which activate the transcription of genes required for DNA synthesis . Additionally, CDK2 is involved in the regulation of DNA replication and repair processes, ensuring the fidelity of cell division .
Dysregulation of CDK2 activity has been implicated in various cancers. Overexpression of CDK2 or its cyclin partners can lead to uncontrolled cell proliferation and tumorigenesis . As a result, CDK2 is considered a potential therapeutic target for cancer treatment. Inhibitors of CDK2 are being developed and tested in clinical trials to evaluate their efficacy in cancer therapy .