Cdk-cyclin complex and its regulators in the cell cycle and cancer
Related
Investigate Cdk-cyclin and its associated protein targets in the cell cycle and cancer with highly cited reagents.
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), growth phase (G1), through DNA replication (S), and finally to cell division (M). Abnormalities in cell cycle control that occur in any of the phases lead to cell cycle arrest and might be associated with cancer1.
Contents
- p21
- MDM2
- Cdk2 (CDKN2, p33)
- Cyclin B1
- Cyclin E1
- Cyclin A1
- Cdc25c
- Cdc6
- Cdk4/6 and cyclin D1/D2
- Retinoblastoma protein (Rb)
p21
p21 directly binds to Cdk-cyclin complexes maintaining Cdk in an inactive state2. Inactive Cdk cannot phosphorylate downstream targets thereby leading to cell cycle arrest3.
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.
| Type | Reagent name | Description | AbID |
| Antibody | Anti-p21 antibody [ER362] | Type: Rabbit monoclonal antibody Reactivity: Hu Applications: WB, IHC-P, Flow Cyt, ICC/IF, IP | ab109520 |
| Anti-p21 antibody [CIP1/823] - BSA and Azide free | Type: Mouse monoclonal antibody Reactivity: Hu Applications: IHC-P, WB, ICC/IF, Flow Cyt | ab212247 |
Click here for the full list of p21 antibodies
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 degradation4.
| Type | Reagent name | Description | AbID |
| Antibody | Anti-MDM2 antibody | Type: Mouse monoclonal Reactivity: Hu, Mo Applications: Flow Cyt, ICC/IF, IHC-P, IHC-Fr, IP, WB, ICC | ab16895 |
Click here for the full list of MDM2 antibodies
Cdk2 (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 repair5.
| 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 | Type: Rabbit monoclonal antibody Reactivity: Hu, Mo, Rt Applications: IHC-P, WB, IP | ab76146 | |
| Anti-CDK2 (phospho T14) antibody | Type: Rabbit monoclonal antibody Reactivity: Hu, Rt, ChHa Applications: WB, IP, IHC-P, ICC | ab68265 | |
| Anti-CDK2 (phospho T160) antibody | Type: Rabbit monoclonal antibody Reactivity: Hu, Mo, Rt Applications: IHC-P, WB | ab194868 |
Click here for the full list of Cdk 2 antibodies
Cyclin B1
Cyclin B1 levels rise during G2 phase facilitating Cdk1-cyclin B1 complex formation6. Cdk1-cyclin B1 is activated by Cdc25 phosphatase7. Cyclin B1 is often found to be overexpressed in certain cancer types.
| Type | Reagent name | Description | AbID |
| Antibody | Anti-Cyclin B1 antibody | Type: Rabbit monoclonal antibody Reactivity: Hu Applications: WB, IHC-P, Flow Cyt, ICC, IP | ab32053 |
| Anti-Cyclin B1 (p S126) antibody | Type: Rabbit monoclonal antibody Reactivity: Hu Applications: WB, IP | ab133439 |
Click here for the full list of Cyclin B1 antibodies
Cdk2-cyclin E1 complex facilitates phosphorylation of retinoblastoma protein (Rb), E2F transcription factor release and DNA S phase entry8.
| Type | Reagent name | Description | AbID |
| Antibody | Anti-Cyclin E1 antibody | Type: Rabbit monoclonal antibody Reactivity: Hu Applications: WB, ICC/IF, Flow Cyt, IP | ab33911 |
Click here for the full list of Cyclin E1 antibodies
Cyclin A1 expression has been reported in several cancers9. p53 activates cyclin A1 promoter. Cdk2-cyclin A1 complex functions in DNA double strand break repair10.
| Type | Reagent name | Description | AbID |
| Antibody | Anti-Cyclin A1/A2 antibody | Type: Rabbit monoclonal antibody Reactivity: Hu Applications: WB, IHC-P, IP | ab185619 |
Click here for the full list of Cyclin A1
Cdc25c
Cdc25 dephosphorylates Y15 and T14 on Cdk2, the rate-limiting step in Cdk activation/cell-cycle progression11.
| 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 |
Click here for the full list of Cdc25c antibodies
Cdc6
CDC6 has been associated with oncogenic activities in many types of cancer12. Protein expression of Cdc6 increases during G1 phase. Cdc6 regulates initiation of DNA replication and its levels are stabilized by Cdk2-cyclin E activity13.
| Type | Reagent name | Description | AbID |
| Antibody | Anti-Cdc6 antibody | Type: Rabbit monoclonal antibody Reactivity: Hu Applications: ICC/IF, WB, IHC-P, Flow Cyt | ab109315 |
| Anti-Cdc6 (phospho S54) antibody | Phosphorylation on S54 prevents Cdc6 from APC/C-dependent proteolysis22. Type: Rabbit monoclonal antibody Reactivity: Hu Applications: WB, ICC/IF, Dot blot | ab75809 | |
| Anti-Cdc6 (phospho S106) antibody | Cdk2-Cyclin E phosphorylation site required to induce G2 arrest23. Type: Rabbit monoclonal antibody Reactivity: Hu Applications: WB | ab76422 | |
| Anti-CRM1 antibody (Nuclear export factor) | CRM1 regulates Cyclin B1 nuclear export and localization10. Type: Rabbit monoclonal antibody Reactivity: Hu, Mo, Rt Applications: IHC-P, Flow Cyt, ICC/IF, WB | ab191081 |
Click here for the full list of Cdc6 antibodies
Cdk4/6 and cyclin D1/2
Required for efficient cell proliferation and playing a role in cancer formation14, kinase activity of Cdk4-cyclin D complex is inhibited by increase in p21 levels13. Cyclin D2 acts as a Cdk2 binding partner in absence of Cdk4 and Cdk616.
| 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 |
Click here for the full list of Cdk4 antibodies
Click here for the full list of Cdk6 antibodies
Click here for the full list of Cyclin D1 antibodies
Click here for the full list of Cyclin D2 antibodies
Retinoblastoma protein (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 progression17. p21 both activates Rb by dephosphorylation and inactives it by degradation, leading to a negative feedback regulation of cell cycle checkpoint.
| Type | Reagent name | Description | AbID |
| Antibody | Anti-Rb binding protein 6 antibody | Type: Rabbit polyclonal antibody Reactivity: Hu, Mo Applications: WB, IHC-P, ICC/IF | ab237514 |
| Anti-Rb binding protein 1 antibody | Type: Rabbit polyclonal antibody Reactivity: Hu Applications: ELISA, WB | ab25913 |
Click here for the full list of Rb antibodies
References
- Casimiro, M., Crosariol, M., Loro, E., Li, Z., & Pestell, R.G. Cyclins and Cell Cycle Control in Cancer and Disease Genes Cancer 3(11-12): 649-657 (2012) Read more
- Harper, J. W. et al. Inhibition of cyclin-dependent kinases by p21. Mol. Biol. Cell 6, 387–400 (1995). Read more
- 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). Read more
- Zhang, Z. et al. MDM2 Is a Negative Regulator of p21WAF1/CIP1, Independent of p53. J. Biol. Chem. 279, 16000–16006 (2004). Read more
- O’Connor, P. M. Mammalian G1 and G2 phase checkpoints. Cancer Surv. 29, 151–82 (1997). Read more
- 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). Read more
- Boutros, R., Dozier, C. & Ducommun, B. The when and wheres of CDC25 phosphatases. Curr. Opin. Cell Biol. 18, 185–91 (2006). Read more
- Dimova, D. K. & Dyson, N. J. The E2F transcriptional network: old acquaintances with new faces. Oncogene 24, 2810–2826 (2005). Read more
- Arsenic, R., Braicu, E. I., … and Ochsenreither, S. Cancer-testis antigen cyclin A1 is broadly expressed in ovarian cancer and is associated with prolonged time to tumor progression after platinum-based therapy BMC Cancer 15:784 (2015) Read more
- Müller-Tidow, C. et al. The cyclin A1-CDK2 complex regulates DNA double-strand break repair. Mol. Cell. Biol. 24, 8917–28 (2004). Read more
- Donzelli, M. & Draetta, G. F. Regulating mammalian checkpoints through Cdc25 inactivation. EMBO Rep. 4, 671–7 (2003). Read more
- 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) Read more
- 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). Read more
- 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). Read more
- Kehn, K. et al. The role of cyclin D2 and p21/waf1 in human T-cell leukemia virus type 1 infected cells. Retrovirology 1, 6 (2004). Read more
- Baker, S. J. & Reddy, E. P. CDK4: A Key Player in the Cell Cycle, Development, and Cancer. Genes Cancer 3, 658–69 (2012). Read more
- Münger, K. & Howley, P. M. Human papillomavirus immortalization and transformation functions. Virus Res. 89, 213–28 (2002). Read more