Cdk-cyclin complex markers

​​p21 directly binds to Cdk-cyclin complexes maintaining Cdk in an inactive state¹. Inactive Cdk cannot phosphorylate downstream targets thereby leading to cell cycle arrest².

Modulating p21 and its associated Cdk target proteins can cause DNA damage, replication stress, and DNA accumulation and contribute to cancer development. Studying DNA changes during cell cycle arrest will help better characterize cell cycle progression and the effect of target modulation in cancer.

MDM2 is a negative regulator of p21, which binds p21 and directs it to proteasome-mediated degradation¹. That's why MDM2 inhibition elevates p21, while its overexpression has the opposite effect.

Cdk 2 is associated with tumor proliferation in multiple cancer types. Binding of p21 to Cdk2-cyclin E complex arrests cells at the G1/S checkpoint. Cdk2 inhibition by p21 is therefore crucial for DNA damage repair¹.

​​Cyclin B1 levels rise during the G2 phase facilitating Cdk1-cyclin B1 complex formation¹. Cdk1-cyclin B1 is activated by Cdc25 phosphatase². 

Cyclin B1 is often found to be overexpressed in certain cancer types. 

Cdk2-cyclin E1 complex facilitates phosphorylation of retinoblastoma protein (Rb), E2F transcription factor release and DNA S phase entry¹. 

Cdc25 dephosphorylates Y15 and T14 on Cdk2, the rate-limiting step in Cdk activation/cell-cycle progression¹.

CDC6 has been associated with oncogenic activities in many types of cancer¹. Protein expression of Cdc6 increases during the G1 phase. Cdc6 regulates the initiation of DNA replication, and its levels are stabilized by Cdk2-cyclin E activity².

The kinase activity of the Cdk4-cyclin D complex is required for efficient cell proliferation and plays a role in cancer formation¹; it is inhibited by an increase in p21 levels². Cyclin D2 acts as a Cdk2 binding partner in the absence of Cdk4 and Cdk6³.

Rb is inactivated following phosphorylation by Cdk2 and Cdk4/6. p21 inhibition of Cdk leads to dephosphorylation and activation of Rb. Rb forms a complex with E2F transcription factor and stalls cell cycle progression¹.