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Professor of Biochemistry
Primary Office: 3130 MERFIowa City, IA 52242
Primary Office Phone: 319-335-7910
Email: email@example.comWeb: Price Laboratory
BS, Dept of Chemistry, North Carolina State UniversityPhD, Dept of Chemistry, Florida State University
Post Doctoral, Dept of Biology, CaltechPost Doctoral, Dept of Chemistry, Caltech
Biosciences Graduate ProgramDepartment of Biochemistry PhDInterdisciplinary Graduate Program in Molecular and Cellular BiologyInterdisciplinary Graduate Program in Translational BiomedicineMedical Scientist Training Program
Understanding how mRNA levels are controlled in eukaryotes requires dissection of the intricate pathway responsible for the synthesis and processing of mRNA. Previously, we obtained evidence for a general eukaryotic transcription regulatory process that controls the number of polymerase molecules that are able to produce full-length mRNAs. We discovered P-TEFb, a cyclin dependent kinase that plays a key role in this elongation control process. The kinase activity of P-TEFb is generally required for eukaryotic gene expression and recent results indicate that cells carefully regulate P-TEFb through an unusual association with a small RNA called 7SK. We are currently engaged in projects to uncover the mechanism of P-TEFb function and how it is regulated. The AIDS virus, HIV, encodes a protein, Tat, that enables the virus to take over the control of P-TEFb. We are studying Tat-transactivation and are examining the mechanism of action of drugs that target this critical step in the HIV life cycle. One such drug, flavopiridol, is in clinical trials as an anti-cancer therapy. We have shown that flavopiridol targets the kinase activity of P-TEFb and this can block the growth of cancer cells and at lower concentrations block HIV replication. Our basic research on factors that influence elongation by RNA polymerase II also uncovered the first RNA polymerase II termination factor, TTF2. Current results indicate that this factor plays a role in mitotic repression of transcription elongation and transcription coupled repair of DNA. Finally, we have begun to develop new in vitro assays to study the mechanistic details of the interaction of RNA processing machinery with the transcription complex. We have shown that 5' capping of mRNAs occurs about 100,000 times more efficiently if transcripts are in elongation complexes. Overall, we use biochemical, molecular and cellular techniques to advance our understanding of the control of RNA polymerase II elongation and how that process influences RNA processing, HIV replication and cancer growth.
Van Duyne R,
El Kouni M,
Effect of mimetic CDK9 inhibitors on HIV-1-activated transcription.
Journal of molecular biology.
2013 February. 425(4):812-29.
PKC phosphorylates HEXIM1 and regulates P-TEFb activity.
Nucleic acids research.
2012 October. 40(18):9160-70.
Transcriptional regulation of the GPX1 gene by TFAP2C and aberrant CpG methylation in human breast cancer.
The Drosophila 7SK snRNP and the essential role of dHEXIM in development.
Nucleic acids research.
2012 July. 40(12):5283-97.
7SK snRNA: a noncoding RNA that plays a major role in regulating eukaryotic transcription.
Wiley interdisciplinary reviews. RNA.
Gdown1 - making a link between Mediator and RNA polymerase II elongation control.
RNA polymerase II elongation control.
Annual review of biochemistry.
Functional association of Gdown1 with RNA polymerase II poised on human genes.
2012 January. 45(1):38-50.
Transcription factor IIS cooperates with the E3 ligase UBR5 to ubiquitinate the CDK9 subunit of the positive transcription elongation factor B.
The Journal of biological chemistry.
2011 February. 286(7):5012-22.
The Role of RNA Polymerase II Elongation Control in HIV-1 Gene Expression, Replication, and Latency.
Genetics research international.
2011. 2011:Article ID. 726901.
Date Last Modified: 06/07/2014 -
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