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Concept
Cyclin-dependent kinase 2
Summary
Cyclin-dependent kinase 2, also known as cell division protein kinase 2, or Cdk2, is an enzyme that in humans is encoded by the CDK2 gene. The protein encoded by this gene is a member of the cyclin-dependent kinase family of Ser/Thr protein kinases. This protein kinase is highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2, also known as Cdk1 in humans. It is a catalytic subunit of the cyclin-dependent kinase complex, whose activity is restricted to the G1-S phase of the cell cycle, where cells make proteins necessary for mitosis and replicate their DNA. This protein associates with and is regulated by the regulatory subunits of the complex including cyclin E or A. Cyclin E binds G1 phase Cdk2, which is required for the transition from G1 to S phase while binding with Cyclin A is required to progress through the S phase. Its activity is also regulated by phosphorylation. Multiple alternatively spliced variants and multiple transcription initiation sites of this gene have been reported. The role of this protein in G1-S transition has been recently questioned as cells lacking Cdk2 are reported to have no problem during this transition.
Original cell-culture based experiments demonstrated cell cycle arrest at the G1-S transition resulting from the deletion of Cdk2. Later experiments showed that Cdk2 deletions lengthened the G1 phase of the cell cycle in mouse embryo fibroblasts. However, they still entered S phase after this period and were able to complete the remaining phases of the cell cycle. When Cdk2 was deleted in mice, the animals remained viable despite a reduction in body size. However, meiotic function of both male and female mice was inhibited. This suggests that Cdk2 is non-essential for the cell cycle of healthy cells, but essential for meiosis and reproduction. Cells in Cdk2 knockout mice likely undergo fewer divisions, contributing to the reduction in body size. Germ cells also stop dividing at prophase of meiosis, leading to reproductive sterility.
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