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.
| Binning, Jennifer M; Smith, Amber M; Hultquist, Judd F et al. (2018) Fab-based inhibitors reveal ubiquitin independent functions for HIV Vif neutralization of APOBEC3 restriction factors. PLoS Pathog 14:e1006830 |
| Huang, Fang; Shao, Wei; Fujinaga, Koh et al. (2018) Bromodomain-containing protein 4-independent transcriptional activation by autoimmune regulator (AIRE) and NF-?B. J Biol Chem 293:4993-5004 |
| Leoz, Marie; Kukanja, Petra; Luo, Zeping et al. (2018) HEXIM1-Tat chimera inhibits HIV-1 replication. PLoS Pathog 14:e1007402 |
| Cary, Daniele C; Peterlin, B Matija (2018) Natural Products and HIV/AIDS. AIDS Res Hum Retroviruses 34:31-38 |
| Ferdin, Jana; Gori?ar, Katja; Dolžan, Vita et al. (2018) Viral protein Nef is detected in plasma of half of HIV-infected adults with undetectable plasma HIV RNA. PLoS One 13:e0191613 |
| Cary, Daniele C; Peterlin, B Matija (2018) Procyanidin trimer C1 reactivates latent HIV as a triple combination therapy with kansui and JQ1. PLoS One 13:e0208055 |
| Peterlin, B Matija; Liu, Pingyang; Wang, Xiaoyun et al. (2017) Hili Inhibits HIV Replication in Activated T Cells. J Virol 91: |
| Tan, Justin L; Fogley, Rachel D; Flynn, Ryan A et al. (2016) Stress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanoma. Mol Cell 62:34-46 |
| Cary, Daniele C; Fujinaga, Koh; Peterlin, B Matija (2016) Euphorbia Kansui Reactivates Latent HIV. PLoS One 11:e0168027 |
| Cary, Daniele C; Fujinaga, Koh; Peterlin, B Matija (2016) Molecular mechanisms of HIV latency. J Clin Invest 126:448-54 |
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