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| Status |
Public on Jun 17, 2015 |
| Title |
Expression profiling of HeLa cell line treated with CDK9 inhibitor |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
CDK9 is the kinase subunit of P-TEFb that enables RNA polymerase (Pol) II to transit from promoter-proximal pausing to productive elongation. Although considerable interest exists in CDK9 as a therapeutic target, little progress has been made due to the lack of highly selective inhibitors. Here, we describe the development of i-CDK9 as such an inhibitor that potently suppresses CDK9 phosphorylation of substrates and causes genome-wide Pol II pausing. While most genes experience reduced expression, MYC and other primary response genes increase expression upon sustained i-CDK9 treatment. Essential for this increase, the bromodomain protein BRD4 captures P-TEFb from 7SK snRNP to deliver to target genes and also enhances CDK9’s activity and resistance to inhibition. Because the i-CDK9-induced MYC expression and binding to P-TEFb compensate for P-TEFb’s loss of activity, only the simultaneous inhibition of CDK9 and MYC can efficiently induce growth arrest and apoptosis of cancer cells, suggesting the potential of a combinatorial treatment strategy.
We used microarrays to examine the global impact on gene expression by imhibiting CDK9 at different time durations.
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| Overall design |
HeLa cell lines treated with CDK9 inhibitor at different time points
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| Contributor(s) |
Yu GK, Lu H, Gao Z, Zhou Q |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Aug 29, 2014 |
| Last update date |
Jun 19, 2015 |
| Contact name |
Zhenhai Gao |
| E-mail(s) |
zgao@incyte.com
|
| Organization name |
Novartis Institute for Biomedical Research
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| Street address |
4560 Horton street
|
| City |
emeryville |
| State/province |
California |
| ZIP/Postal code |
94608 |
| Country |
USA |
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| Platforms (1) |
| GPL18756 |
Affymetrix HG-U133_PLUS_2[CDF: HGU133Plus2_Hs_ENTREZG_14.1.0] |
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| Samples (18)
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| This SubSeries is part of SuperSeries: |
| GSE60954 |
Expression profiling and Pol II occupancy of HeLa cell line treated with CDK9 inhibitor |
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| Relations |
| BioProject |
PRJNA260843 |
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