scholarly journals Activation of HIV-1 with Nanoparticle-Packaged Small Molecule Protein Phosphatase-1-Targeting Compound

2015 ◽  
Vol 83 (3) ◽  
pp. 535-548 ◽  
Author(s):  
Kahli A. Smith
Keyword(s):  
Small Molecule ◽  
Protein Phosphatase ◽  
Protein Phosphatase 1 ◽  
Hiv 1

scholarly journals 1E7-03, a Small Molecule Targeting Host Protein Phosphatase-1, Inhibits HIV-1 Transcription

2014 ◽  
pp. n/a-n/a ◽  
Author(s):  
Tatyana Ammosova ◽  
Maxim Platonov ◽  
Andrei Ivanov ◽  
Yasemin Saygideğer Kont ◽  
Namita Kumari ◽  
...  
Keyword(s):  
Small Molecule ◽  
Protein Phosphatase ◽  
Host Protein ◽  
Protein Phosphatase 1 ◽  
Hiv 1

scholarly journals Inhibition of HIV-1 infection in humanized mice and metabolic stability of protein phosphatase-1-targeting small molecule 1E7-03

Oncotarget ◽  
2017 ◽  
Vol 8 (44) ◽  
pp. 76749-76769 ◽  
Author(s):  
Xionghao Lin ◽  
Namita Kumari ◽  
Catherine DeMarino ◽  
Yasemin Saygideğer Kont ◽  
Tatiana Ammosova ◽  
...  
Keyword(s):  
Small Molecule ◽  
Protein Phosphatase ◽  
Metabolic Stability ◽  
Protein Phosphatase 1 ◽  
Humanized Mice ◽  
Hiv 1

scholarly journals Protein Phosphatase 1–Targeting Small-Molecule C31 Inhibits Ebola Virus Replication

2018 ◽  
Vol 218 (suppl_5) ◽  
pp. S627-S635 ◽  
Author(s):  
Tatiana Ammosova ◽  
Colette A Pietzsch ◽  
Yasemin Saygideğer ◽  
Andrey Ilatovsky ◽  
Xionghao Lin ◽  
...  
Keyword(s):  
Virus Replication ◽  
Small Molecule ◽  
Protein Phosphatase ◽  
Ebola Virus ◽  
Protein Phosphatase 1

Non-Competitive Protein Phosphatase-1 Inhibitors Prevent Sickling of SS RBCs.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4038-4038
Author(s):  
Jerod Hairston ◽  
Keon Combi ◽  
Altreisha Foster ◽  
Bak Kim ◽  
Victor R. Gordeuk ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Cultured Cells ◽  
Conflicts Of Interest ◽  
Protein Phosphatase 1 ◽  
Cell Protein ◽  
Trypan Blue Exclusion ◽  
Future Design ◽  
Small Molecular Inhibitors ◽  
Hiv 1

Abstract Abstract 4038 Poster Board III-974 Protein phosphatase-1 (PP1) has been implicated in the regulation of KCC (K:Cl) transporters, which transport K+ and Cl- ions from red blood cells (RBCs) and in the setting of sickle cell disease may contribute to RBC dehydration and sickling. We have studied host cell protein phosphatase-1 (PP1) in the context of HIV-1 replication and designed novel small molecule non-competitive inhibitors of PP1 that are efficient in the inhibition of HIV-1 but not toxic for cultured cells. We analyzed the effect of our novel non-competitive PP1 inhibitors and the conventional competitive PP1 inhibitor, ocadaic acid, on the sickling of hemoglobin SS RBCs in vitro. We cultured hemoglobin SS RBCs overnight at 1% O2 in the presence of the PP1 inhibitors and then photographed the RBCs and counted the percentage of sickled RBCs. We found that the non-competitive PP1 inhibitor, 1E7-04 prevented RBC sickling by 40% at 10 mM concentration. The 1E7-04 was not toxic at 10 mM concentration for cultured CEM T cells as determined by trypan blue exclusion assay using an automatic cell counter. Our study suggests that small molecular inhibitors of PP1 might be candidates for the future design of anti-sickling drugs. Acknowledgments. This work was supported by NHLBI grant U54HL090508-02; NHLBI grant R25 HL003679-08 from the National Institute of Helath and The Office of Research on Minority Health and by U.S. Civilian Research & Development Foundation grant. Disclosures: No relevant conflicts of interest to declare.

Hypoxia Inhibits HIV-1 Transcription.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1305-1305
Author(s):  
Sergei Nekhai ◽  
Charles Sharroya ◽  
Tatyana Ammosova ◽  
Xiaomei Nui ◽  
Marina Jerebtsova ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Oxygen Tension ◽  
Protein Phosphatase ◽  
Tissue Oxygenation ◽  
Protein Phosphatase 1 ◽  
Tat Protein ◽  
Cyclin T1 ◽  
Hiv Transcription ◽  
Hiv 1

Abstract The hypoxic response is an important component of the body’s reaction to impaired tissue oxygenation associated with the anemia and vasoocclusive episodes of sickle cell disease (SCD). It has been reported that HIV infection progresses relatively slowly in patients with SCD (Am J Hematol1998;59:199–207). HIV-1 Tat protein promotes transcription of HIV-1 genes by inducing CDK9/cyclin T1 to phosphorylate the C-terminal domain of RNA polymerase-II. Our previous studies indicate that protein phosphatase-1 (PP1) promotes Tat-induced HIV-1 transcription (J Biol Chem2003;278:32189–941), apparently by interacting with HIV-1 Tat, for disruption of this interaction prevents induction of transcription (J Biol Chem2005;280:36364–71). Recently PP1 activity was shown to be decreased in hypoxia in part through increased association of PP1 with NIPP1 (J Cell Physiol 2006 Jul 6; Epub ahead of print). We hypothesized that decreased PP1 activity during hypoxia would reduce HIV-1 transcription and viral replication, and we have obtained experimental results consistent with this hypothesis.Increased expression of nuclear inhibitor of PP1 (NIPP1) was associated with inhibition of HIV-1 transcription and viral replication.Low oxygen tension (3%–6% O2) was associated with transient inhibition of HIV-1 transcription in transfected 293T and HeLa cells.Low oxygen tension was associated with inhibition of HIV-1 transcription in CEM T cells infected with pseudotyped HIV-1 virus. We are now planning to examine the possible role of altered PP1 activity in the observed inhibition of HIV-1 transcription during hypoxia. Thus, a clinical insight from patients with SCD has pointed the way to investigating the influence of hypoxia on HIV transcription. An improved understanding of how oxygen status influences viral activation versus inactivation might open new possibilities for treatment of hidden HIV-1 reservoirs that harbor non-replicating HIV-1 virus.

scholarly journals Nuclear Protein Phosphatase-1 Regulates HIV-1 Transcription

2003 ◽  
Vol 278 (34) ◽  
pp. 32189-32194 ◽  
Author(s):  
Tatyana Ammosova ◽  
Marina Jerebtsova ◽  
Monique Beullens ◽  
Yaroslav Voloshin ◽  
Patricio E. Ray ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Nuclear Protein ◽  
Protein Phosphatase 1 ◽  
Hiv 1

scholarly journals Small Molecules Targeted to a Non-Catalytic “RVxF” Binding Site of Protein Phosphatase-1 Inhibit HIV-1

PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. e39481 ◽  
Author(s):  
Tatiana Ammosova ◽  
Maxim Platonov ◽  
Venkat R. K. Yedavalli ◽  
Yuri Obukhov ◽  
Victor R. Gordeuk ◽  
...  
Keyword(s):  
Small Molecules ◽  
Binding Site ◽  
Protein Phosphatase ◽  
Protein Phosphatase 1 ◽  
Hiv 1

scholarly journals Expression of a Protein Phosphatase 1 Inhibitor, cdNIPP1, Increases CDK9 Threonine 186 Phosphorylation and Inhibits HIV-1 Transcription

2010 ◽  
Vol 286 (5) ◽  
pp. 3798-3804 ◽  
Author(s):  
Tatiana Ammosova ◽  
Venkat R. K. Yedavalli ◽  
Xiaomei Niu ◽  
Marina Jerebtsova ◽  
Aleyde Van Eynde ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Protein Phosphatase 1 ◽  
Hiv 1

scholarly journals Nuclear Targeting of Protein Phosphatase-1 by HIV-1 Tat Protein

2005 ◽  
Vol 280 (43) ◽  
pp. 36364-36371 ◽  
Author(s):  
Tatyana Ammosova ◽  
Marina Jerebtsova ◽  
Monique Beullens ◽  
Bart Lesage ◽  
Angela Jackson ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Protein Phosphatase ◽  
Protein Phosphatase 1 ◽  
Tat Protein ◽  
Nuclear Targeting ◽  
Cyclin T1 ◽  
Immunodeficiency Virus ◽  
Hiv 1

Transcription of human immunodeficiency virus (HIV)-1 genes is activated by HIV-1 Tat protein, which induces phosphorylation of the C-terminal domain of RNA polymerase-II by CDK9/cyclin T1. We previously showed that Tat-induced HIV-1 transcription is regulated by protein phosphatase-1 (PP1). In the present study we demonstrate that Tat interacts with PP1 and that disruption of this interaction prevents induction of HIV-1 transcription. We show that PP1 interacts with Tat in part through the binding of Val36 and Phe38 of Tat to PP1 and that Tat is involved in the nuclear and subnuclear targeting of PP1. The PP1 binding mutant Tat-V36A/F38A displayed a decreased affinity for PP1 and was a poor activator of HIV-1 transcription. Surprisingly, Tat-Q35R mutant that had a higher affinity for PP1 was also a poor activator of HIV-1 transcription, because strong PP1 binding competed out binding of Tat to CDK9/cyclin T1. Our results suggest that Tat might function as a nuclear regulator of PP1 and that interaction of Tat with PP1 is critical for activation of HIV-1 transcription by Tat.

Sign in / Sign up

Export Citation Format

Share Document