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- Since applications vary, each investigator should titrate the reagent to obtain optimal results.
- Please refer to www.bdbiosciences.com/us/s/resources for technical protocols.
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The Cdk4 kinase is a cell cycle-regulated cyclin-dependent kinase that associates with cyclins D1, D2, and D3. In macrophages and fibroblasts, Cdk4-Cyclin D1 complexes are predominant. Much like Cdk2 and Cdc2, the activity of Cdk4 is regulated by association with its respective kinase and by phosphorylation of specific threonine residues. The cdk-activating kinase (CAK) is a regulator of cdk-cyclin activity by virtue of its ability to phosphorylate single threonine residues on Cdk2, Cdc2, and Cdk4. Active Cdk4-Cyclin D1 complexes are capable of phosphorylating the retinoblastoma gene product (pRb), but not histone H1 or casein. Formation of the Cdk4-Cyclin D holoenzyme and phosphorylation of the catalytic subunit appear to be independently regulated. Therefore, other cellular factors may be necessary for stabilization of this protein complex in order to facilitate the phosphorylation of Cdk4. An inhibitor of Cdk4 kinase activity, known as p16, has been identified and partially characterized. The p16 gene appears to be altered in many tumors, suggesting that this is a tumor suppressor gene. It is thought that p16 inhibition of Cdk4-Cyclin D interferes with cell cycle progression by preventing phosphorylation of pRb by Cdk4 and the subsequent release of factors that activate transcription.
This antibody is routinely tested by western blot analysis. Other applications were tested at BD Biosciences Pharmingen during antibody development only or reported in the literature.
研发参考 (5)
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Angus SP, Wheeler LJ, Ranmal SA, et al. Retinoblastoma tumor suppressor targets dNTP metabolism to regulate DNA replication. J Biol Chem. 2002; 277(46):44376-44384. (Biology: Western blot). 查看参考
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Bagui TK, Jackson RJ, Agrawal D, Pledger WJ. Analysis of cyclin D3-cdk4 complexes in fibroblasts expressing and lacking p27(kip1) and p21(cip1). Mol Cell Biol. 2000; 20(23):8748-8757. (Biology: Immunoprecipitation, Western blot). 查看参考
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Kato J, Matsushime H, Hiebert SW, Ewen ME, Sherr CJ. Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent kinase CDK4. Genes Dev. 1993; 7(3):331-342. (Biology). 查看参考
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Saitoh H, Pizzi MD, Wang J. Perturbation of SUMOlation enzyme Ubc9 by distinct domain within nucleoporin RanBP2/Nup358. J Biol Chem. 2002; 277(7):4755-4763. (Biology: Immunofluorescence). 查看参考
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Xiong Y, Zhang H, Beach D. D type cyclins associate with multiple protein kinases and the DNA replication and repair factor PCNA. Cell. 1992; 71(3):505-514. (Biology). 查看参考
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