The goal of this project is to define structural and functional aspects of CTD kinases that are critical for HIV replication. They are CycT1:CDK9 (P-TEFb), CycL1/L2:CDK11, CycK:CDK12 and CycK:CDK13. P-TEFb is the co-activator of NF-kB and Tat. CDK11 and CDK12 play critical roles in HIV 3' end formation, i.e. cleavage and polyadenylation. CDK13 is important for HIV mRNA splicing. Studies of their regulation in cells and in HIV silencing and reactivation are major goals of this proposal. In addition, we are developing sensitive assays for the release of P-TEFb from its inactive 7SK snRNP in cells, which will be adapted for the analysis of compounds that can be used to reactivate HIV from latency as well as treat many different forms of cancer and inflammation. These studies will inform all strategies aimed at reducing and/or eliminating the reservoir of HIV in infected individuals.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI125104-04
Application #
9634018
Study Section
AIDS Molecular and Cellular Biology Study Section (AMCB)
Program Officer
Refsland, Eric William
Project Start
2016-02-01
Project End
2021-01-31
Budget Start
2019-02-01
Budget End
2020-01-31
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118
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