The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Flavopiridol Inhibits P-TEFb and Blocks HIV-1 Replication
Open accessAbstract
Flavopiridol (L86-8275, HMR1275) is a cyclin-dependent kinase (Cdk) inhibitor that is in clinical trials as a cancer treatment because of its antiproliferative properties. We found that the flavonoid potently inhibited transcription by RNA polymerase II in vitro by blocking the transition into productive elongation, a step controlled by P-TEFb. The ability of P-TEFb to phosphorylate the carboxyl-terminal domain of the large subunit of RNA polymerase II was inhibited by flavopiridol with a K(i) of 3 nm. Interestingly, the drug was not competitive with ATP. P-TEFb composed of Cdk9 and cyclin T1 is a required cellular cofactor for the human immunodeficiency virus (HIV-1) transactivator, Tat. Consistent with its ability to inhibit P-TEFb, flavopiridol blocked Tat transactivation of the viral promoter in vitro. Furthermore, flavopiridol blocked HIV-1 replication in both single-round and viral spread assays with an IC(50) of less than 10 nm.
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[6] Statistical analysis of enzyme kinetic data
Wallace Cleland, W. (1979) · Methods in Enzymology · doi:10.1016/0076-6879(79)63008-2 · Cited by 1,984
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Exploiting Chemical Libraries, Structure, and Genomics in the Search for Kinase Inhibitors
Gray, N. S., Wodicka, L., Thunnissen, A.-M. W. H., Norman, T. C., Kwon, S., Espinoza, F. H., Morgan, D. O., Barnes, G., LeClerc, S., Meijer, L., et al. (1998) · Science · doi:10.1126/science.281.5376.533 · Cited by 808
Transcription elongation factor P-TEFb is required for HIV-1 Tat transactivation in vitro
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Self-citationP-TEFb, a Cyclin-Dependent Kinase Controlling Elongation by RNA Polymerase II
Price, D. H. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.8.2629-2634.2000 · Cited by 679
Self-citationControl of RNA Polymerase II Elongation Potential by a Novel Carboxyl-terminal Domain Kinase
Marshall, N. F., Peng, J., Xie, Z., & Price, D. H. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.43.27176 · Cited by 662
Self-citationMarshall, N. F., & Price, D. H. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.21.12335 · Cited by 560
Self-citationP-TEFb kinase is required for HIV Tat transcriptional activation in vivo and in vitro
Mancebo, H. S. Y., Lee, G., Flygare, J., Tomassini, J., Luu, P., Zhu, Y., Peng, J., Blau, C., Hazuda, D., Price, D., et al. (1997) · Genes & Development · doi:10.1101/gad.11.20.2633 · Cited by 544
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Cited by
c-Myc Regulates Transcriptional Pause Release
Rahl, P. B., Lin, C. Y., Seila, A. C., Flynn, R. A., McCuine, S., Burge, C. B., Sharp, P. A., & Young, R. A. (2010) · Cell · doi:10.1016/j.cell.2010.03.030 · Cited by 1,279
Cyclin-Dependent Kinase Pathways As Targets for Cancer Treatment
Shapiro, G. I. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2005.03.7689 · Cited by 1,036
Inhibiting eukaryotic transcription: which compound to choose? How to evaluate its activity
Bensaude, O. (2011) · Transcription · doi:10.4161/trns.2.3.16172 · Cited by 574
Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation
Olson, C. M., Jiang, B., Erb, M. A., Liang, Y., Doctor, Z. M., Zhang, Z., Zhang, T., Kwiatkowski, N., Boukhali, M., Green, J. L., et al. (2018) · Nature Chemical Biology · doi:10.1038/nchembio.2538 · Cited by 552
Blazek, D., Kohoutek, J., Bartholomeeusen, K., Johansen, E., Hulinkova, P., Luo, Z., Cimermancic, P., Ule, J., & Peterlin, B. M. (2011) · Genes & Development · doi:10.1101/gad.16962311 · Cited by 522
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Metadata
- Authors
- Chao, S.-H., Fujinaga, K., Marion, J. E., Taube, R., Sausville, E. A., Senderowicz, A. M., Peterlin, B. M., & Price, D. H.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-09
- Volume
- 275
- Issue
- 37
- Pages
- 28345-28348
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2147347134
- Cited by
- 455
- References
- 31
- FWCI
- 9.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Chao, S.-H., Fujinaga, K., Marion, J. E., Taube, R., Sausville, E. A., Senderowicz, A. M., Peterlin, B. M., & Price, D. H. (2000). Flavopiridol Inhibits P-TEFb and Blocks HIV-1 Replication. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.c000446200
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