Cdk-cylin complex and its effectors

Investigate Cdk-cyclin and its associating protein targets in cell cycle and cancer with highly cited reagents.

Cdk (cyclin-dependent kinase) associates with cyclins to play a crucial role in cell cycle progression. 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. 

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Contents

• Cdk1 (Cdc2, p34^Cdc2)
• Cyclin B1
• Cdk2 (CDKN2, p33)
• Cyclin E1
• Cyclin A1
• Cdc25c
• Cdc6
• Cdk4/6 and cyclin D1/D2
• Retinoblastoma protein (Rb)
• MDM2
• p21 cell cycle analysis

​​​Cdk1 (Cdc2, p34^Cdc2​)

Cdk1 interacts with cyclin B to form an active heterodimer³. Cdk1-cyclin B1 complex progresses the cell cycle through G2/M mitotic phase. Uncontrolled Cdk1 activation can lead to apoptosis².
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Click here for the full list of Cdk inhibitors

Cyclin B1

​​Cyclin B1 levels rise during G2 phase facilitating Cdk1-cyclin B1 complex formation⁶. Cdk1-cyclin B1 is activated by Cdc25 phosphatase⁷.
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Click here for conjugated Cdk antibodies

Cdk 2 (CDKN2, p33)

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 repair¹¹.

Type	Reagent name	Description	AbID
Antibody	Anti-Cdk2 antibody​	Type: Rabbit monoclonal antibody Reactivity: Hu, Mo, Rt Applications: ICC/IF, IP, WB, Flow Cyt, IHC-P	ab32147
	Anti-CDK2 (phospho Y15) antibody	Y15: Inhibitory phosphorylation site by Wee1 kinase12. Type: Rabbit monoclonal antibody Reactivity: Hu, Mo, Rt Applications: IHC-P, WB, IP	ab76146
	Anti-CDK2 (phospho T14) antibody	T14: Inhibitory phosphorylation site by Wee1 kinase12. Type: Rabbit monoclonal antibody Reactivity: Hu, Rt, ChHa Applications: WB, IP, IHC-P, ICC	ab68265
	Anti-CDK2 (phospho T160) antibody	T160: Phosphorylation that stabilizes the Cdk2-cyclin complex12. Type: Rabbit monoclonal antibody Reactivity: Hu, Mo, Rt ​Applications: IHC-P, WB	ab194868
Small molecule compound	Flavopiridol (Cdk2 inhibitor)	Potent inhibitor Cdk2 kinase activity (IC50 = 100 nM at 400 μM ATP)13.	ab141300
	Roscovitine (Cdk2 inhibitor)	Potent and selective inhibitor of Cdk2, Cdk5, Cdc2. Exhibits IC50 = 0.7 μM for Cdk2/cyclin A, Cdk2/cyclin E14.	ab141847

Cyclin E1 

Cdk2-cyclin E1 complex facilitates phosphorylation of retinoblastoma protein (Rb), E2F transcription factor release and DNA S phase entry¹⁵. 

Cyclin A1

p53 activates cyclin A1 promoter. Cdk2-cyclin A1 complex functions in DNA double strand break repair¹⁷.

Cdc25c 

Cdc25 dephosphorylates Y15 and T14 on Cdk2, the rate-limiting step in Cdk activation/cell-cycle progression¹⁸.

Type	Reagent name	Description	AbID
Antibody	Anti-Cdc25C antibody​	Type: Rabbit monoclonal antibody Reactivity: Hu Applications: WB, IHC-P, ICC/IF, Flow Cyt, IP	ab32444
Small molecule compound	NSC 663284 (Cdc25 inhibitor)	Potent and selective inhibitor of Cdc25 (Ki = 89 nM for Cdc25C)19.	ab144408
	Gossypin (Cdc25 activator)	Induces G2/M arrest and inhibits cell proliferation via Chk1 phosphorylation of Cdc25C20.	ab145623
Lysate	Cdc25C lysate	Cdc25C overexpression 293T lysate suitable for WB as a control. Concentration: 100 µl at 1.7 mg/ml (1x sample buffer)	ab94219

Cdc6

Protein expression of Cdc6 increases during G1 phase. Cdc6 regulates initiation of DNA replication and its levels are stabilized by Cdk2-cyclin E activity²¹.

Cdk4/6 and cyclin D1/2

Required for efficient cell proliferation and plays a role in tumorigenesis²⁵. Kinase activity of Cdk4-cyclin D complex is inhibited by increase in p21 levels²⁶. Cyclin D2 acts as a Cdk2 binding partner in absence of Cdk4 and Cdk6²⁷.

Type	Reagent name	Description	AbID
Antibody	Anti-Cdk4 antibody​	Type: Rabbit monoclonal antibody Reactivity: Hu Applications: WB, IHC-P, Flow Cyt, ICC/IF	ab108357
	Anti-Cdk6 antibody	Type: Rabbit monoclonal antibody Reactivity: Hu Applications: Flow Cyt, ICC/IF, IHC-P, WB	ab124821
	Anti-Cyclin D1 antibody	Type: Rabbit monoclonal antibody Reactivity: Hu, Mo, Rt Applications: WB, IP, ICC/IF, IHC-P	ab134175
	Anti-Cyclin D2 antibody	Type: Rabbit monoclonal antibody Reactivity: Hu Applications: ICC/IF, IP, WB	ab207604
Kit	Cyclin D1 SimpleStep ELISA® kit	Quantitatively measure cyclin D1 protein in human cell and tissue extract samples. Reactivity: Hu Range: 187 pg/ml - 12000 pg/ml; Method: Colorimetric	ab214571
Small molecule compound	Palbociclib (Cdk4/6 inhibitor)	Highly potent Cdk4/6 inhibitor (IC50 = 11 nM and 16 nM for Cdk4/6)28.	ab218118
	Fascaplysin (Cdk4 inhibitor)	Potent, selective ATP-competitive CDK4 inhibitor (IC50 = 350 nM)29.	ab146177

Retinoblastoma protein (Rb)

Rb is inactivated following phosphorylated 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 progression³⁰. p21 can negatively regulate Rb stalling of cell cycle via a feedback loop³¹.

MDM2 

A negative regulator of p21. MDM2 inhibition elevates p21 while its overexpression has the opposite effect. MDM2 binds p21 and directs it to proteasome-mediated degradation³⁵.

p21 cell cycle analysis

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

Click here for the cell proliferation guide

References

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