Cell division and apoptosis are key aspects of cancer biology. Cdk (cyclin-dependent kinase) associates with cyclins to form Cdk-cyclin complexes, which play a crucial role in cell cycle progression. ​

The Cdk-cyclin complexes regulate a series of events that lead cells from a resting state (G0), the growth phase (G1), through DNA replication (S), and finally to cell division (M). Abnormalities in cell cycle control that occur in any phase lead to cell cycle arrest and might be associated with cancer1.

This guide recommends the most suitable antibodies to study Cdk-cyclin and its regulators in cell cycle progression and cancer.

p21

​​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.

We recommend

KO validated Anti-p21 antibody [ER362] (ab109520)

Anti-p21 antibody [CIP1/823] - BSA and Azide free (ab212247)

Browse all p21 antibodies

References

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MDM2

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.

We recommend

Anti-MDM2 antibody (ab16895)

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References

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Cdk2

Alternative names CDKN2, p33

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.

We recommend

KO Validated Anti-Cdk2 antibody (ab32147)

Anti-CDK2 (phospho Y15) antibody (ab76146)

Anti-CDK2 (phospho T14) antibody (ab68265)

Anti-CDK2 (phospho T160) antibody (ab194868)

Browse all Cdk2 antibodies

References

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Cyclin B1

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.

We recommend

KO Validated Anti-Cyclin B1 antibody (ab32053)

Anti-Cyclin B1 (p S126) antibody (ab133439)

Browse all Cyclin B1 antibodies

References

View 2 references for Cyclin B1

Cyclin E1

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

We recommend

KO Validated Anti-Cyclin E1 antibody (ab33911)

Browse all Cycle E1 antibodies

References

View 1 reference for Cyclin E1

Cdc25c

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

We recommend

KO Validated Anti-Cdc25C antibody (ab32444)

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References

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Cdc6

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.

We recommend

Anti-Cdc6 antibody (ab109315)

Anti-Cdc6 (phospho S54) antibody (ab75809)

Anti-Cdc6 (phospho S106) antibody (ab76422)

Anti-CRM1 antibody (Nuclear export factor) (ab191081)

Browse all Cdc6 antibodies

References

View 2 references for Cdc6

Cdk4/6 and Cyclin D1/2

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.

We recommend

KO Validated Anti-Cdk4 antibody (ab108357)

KO Validated Anti-Cdk6 antibody (ab124821)

Anti-Cyclin D1 antibody (ab134175)

Anti-Cyclin D2 antibody [EPR19659] (ab207604)

Cdk4 antibodies

Cdk6 antibodies

Cyclin D1 antibodies

Cyclin D2 antibodies

References

View 3 references for Cdk4/6 and Cyclin D1/2

Retinoblastoma protein

Alternative names Rb

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.

We recommend

Anti-Retinoblastoma binding protein 6 antibody (ab237514)

Browse all Rb antibodies

References

View 1 reference for Retinoblastoma protein

References

p21

Harper, J. W., et. al. Inhibition of cyclin-dependent kinases by p21. Mol. Biol. Cell  6  ,387-400 (1995)

Charrier-Savournin, F. B., et. al. p21-Mediated nuclear retention of cyclin B1-Cdk1 in response to genotoxic stress. Mol. Biol. Cell  15  ,3965-76 (2004)

MDM2

Zhang, Z. , et al. MDM2 Is a Negative Regulator of p21WAF1/CIP1, Independent of p53. J. Biol. Chem.  279  ,16000-16006 (2004)

Cdk2

O’Connor, P. M. Mammalian G1 and G2 phase checkpoints. Cancer Surv  29  ,151-182 (1997)

Cyclin B1

Pines, J. & , Hunter, T. Isolation of a human cyclin cDNA: evidence for cyclin mRNA and protein regulation in the cell cycle and for interaction with p34cdc2. Cell  58  ,833-46 (1989)

Boutros, R.,, Dozier, C. , & Ducommun, B. The when and wheres of CDC25 phosphatases. Curr. Opin. Cell Biol.  18  ,185-91 (2006)

Cyclin E1

Dimova, D. K. , & Dyson, N. J. The E2F transcriptional network: old acquaintances with new faces. Oncogene  24  ,2810-2826 (2005)

Cdc25c

Donzelli, M., & Draetta, G. F. Regulating mammalian checkpoints through Cdc25 inactivation. EMBO Rep  4  ,671-677 (2003)

Cdc6

Sideridou, M.,, Zakopoulou, R.,, and Gorgoulis, V. G Cdc6 expression represses E-cadherin transcription and activates adjacent replication origins J Cell Biol  195(&)  ,1123-1140 (2011)

Duursma, A. M. , & Agami, R. CDK-Dependent Stabilization of Cdc6: Linking Growth and Stress Signals to Activation of DNA Replication. Cell Cycle  4  ,1725-1728 (2005)

Cdk4/6 and Cyclin D1/2

Cole, A. M., et al. Cyclin D2-cyclin-dependent kinase 4/6 is required for efficient proliferation and tumorigenesis following Apc loss. Cancer Res.  70  ,8149-58 (2010)

Duursma, A. M. , & Agami, R. CDK-Dependent Stabilization of Cdc6: Linking Growth and Stress Signals to Activation of DNA Replication. Cell Cycle  4  ,1725-1728 (2005)

Baker, S. J. &, Reddy, E. P. CDK4: A Key Player in the Cell Cycle, Development, and Cancer. Genes Cancer  3  ,658-69 (2012)

Retinoblastoma protein

Münger, K. & , Howley, P. M. Human papillomavirus immortalization and transformation functions. Virus Res.  89  ,213-28 (2002)