Sergei Nekhai

Summary

Affiliation: Howard University
Country: USA

Publications

  1. pmc CDK13, a new potential human immunodeficiency virus type 1 inhibitory factor regulating viral mRNA splicing
    Reem Berro
    Department of Biochemistry and Microbiology, The George Washington University Medical Center, 2300 I St NW, Washington, DC 20037, USA
    J Virol 82:7155-66. 2008
  2. pmc Protein phosphatase-1 activates CDK9 by dephosphorylating Ser175
    Tatiana Ammosova
    Center for Sickle Cell Disease, Howard University, Washington, DC, United States of America
    PLoS ONE 6:e18985. 2011
  3. pmc Small molecules targeted to a non-catalytic "RVxF" binding site of protein phosphatase-1 inhibit HIV-1
    Tatiana Ammosova
    Center for Sickle Cell Disease, Howard University, Washington, DC, United States of America
    PLoS ONE 7:e39481. 2012
  4. pmc Reduced sensitivity of the ferroportin Q248H mutant to physiological concentrations of hepcidin
    Sergei Nekhai
    Center for Sickle Cell Disease, Department of Medicine, Howard University, Washington, DC, USA
    Haematologica 98:455-63. 2013
  5. ncbi Therapies for HIV with RNAi
    Sergei Nekhai
    Howard University, Center for Sickle Cell Disease, 2121 Georgia Ave NW, Washington, DC 20059, USA
    Curr Opin Mol Ther 8:52-61. 2006
  6. ncbi Transcriptional and post-transcriptional regulation of HIV-1 gene expression: role of cellular factors for Tat and Rev
    Sergei Nekhai
    Center for Sickle Cell Disease and Department of Biochemistry and Molecular Biolology, Howard University, NW Washington, DC 20059, USA
    Future Microbiol 1:417-26. 2006
  7. ncbi Regulation of HIV-1 transcription by protein phosphatase 1
    Sergei Nekhai
    Center for Sickle Cell Disease, Howard University, Washington, DC 20059, USA
    Curr HIV Res 5:3-9. 2007
  8. ncbi A novel anticancer agent ARC antagonizes HIV-1 and HCV
    S Nekhai
    Center for Sickle Cell Disease, Howard University College of Medicine, Washington, DC, USA
    Oncogene 26:3899-903. 2007
  9. pmc Dephosphorylation of CDK9 by protein phosphatase 2A and protein phosphatase-1 in Tat-activated HIV-1 transcription
    Tatyana Ammosova
    Center for Sickle Cell Disease, Howard University, 2121 Georgia Ave, N W Washington, DC 20059, USA
    Retrovirology 2:47. 2005
  10. ncbi Nuclear targeting of protein phosphatase-1 by HIV-1 Tat protein
    Tatyana Ammosova
    Center for Sickle Cell Disease, Howard University, Washington, DC 20059, USA
    J Biol Chem 280:36364-71. 2005

Collaborators

Detail Information

Publications44

  1. pmc CDK13, a new potential human immunodeficiency virus type 1 inhibitory factor regulating viral mRNA splicing
    Reem Berro
    Department of Biochemistry and Microbiology, The George Washington University Medical Center, 2300 I St NW, Washington, DC 20037, USA
    J Virol 82:7155-66. 2008
    ..Using small interfering RNA against CDK13, we show that silencing of CDK13 leads to a significant increase in virus production. Finally, we demonstrate that CDK13 mediates its effect on splicing through the phosphorylation of ASF/SF2...
  2. pmc Protein phosphatase-1 activates CDK9 by dephosphorylating Ser175
    Tatiana Ammosova
    Center for Sickle Cell Disease, Howard University, Washington, DC, United States of America
    PLoS ONE 6:e18985. 2011
    ..Collectively, our results point to CDK9 Ser175 as novel PP1-regulatory site which dephosphorylation upregulates CDK9 activity and contribute to the activation of HIV-1 transcription...
  3. pmc Small molecules targeted to a non-catalytic "RVxF" binding site of protein phosphatase-1 inhibit HIV-1
    Tatiana Ammosova
    Center for Sickle Cell Disease, Howard University, Washington, DC, United States of America
    PLoS ONE 7:e39481. 2012
    ..This proof-of-principle study can serve as a starting point for the development of novel antiviral drugs that target the interface of HIV-1 viral proteins with their host partners...
  4. pmc Reduced sensitivity of the ferroportin Q248H mutant to physiological concentrations of hepcidin
    Sergei Nekhai
    Center for Sickle Cell Disease, Department of Medicine, Howard University, Washington, DC, USA
    Haematologica 98:455-63. 2013
    ..ClinicalTrials.gov Identifier:NCT00011648)...
  5. ncbi Therapies for HIV with RNAi
    Sergei Nekhai
    Howard University, Center for Sickle Cell Disease, 2121 Georgia Ave NW, Washington, DC 20059, USA
    Curr Opin Mol Ther 8:52-61. 2006
    ..The problem with the delivery of RNA duplexes to the target cells and the strategies used by HIV-1 to escape inhibition by RNAi are also discussed...
  6. ncbi Transcriptional and post-transcriptional regulation of HIV-1 gene expression: role of cellular factors for Tat and Rev
    Sergei Nekhai
    Center for Sickle Cell Disease and Department of Biochemistry and Molecular Biolology, Howard University, NW Washington, DC 20059, USA
    Future Microbiol 1:417-26. 2006
    ..Rev primarily functions to export unspliced and partially spliced viral RNAs from the nucleus into the cytoplasm. For this activity, Rev cooperates with cellular transport protein CRM1 and RNA helicases DDX1 and DDX3, amongst others...
  7. ncbi Regulation of HIV-1 transcription by protein phosphatase 1
    Sergei Nekhai
    Center for Sickle Cell Disease, Howard University, Washington, DC 20059, USA
    Curr HIV Res 5:3-9. 2007
    ..We also present a computer model of Tat-PP1 complex that might be useful for future drug design in anti-HIV-1 therapeutics...
  8. ncbi A novel anticancer agent ARC antagonizes HIV-1 and HCV
    S Nekhai
    Center for Sickle Cell Disease, Howard University College of Medicine, Washington, DC, USA
    Oncogene 26:3899-903. 2007
    ..Together, our data indicate that ARC could be a promising candidate for the development of antiviral therapeutics against HIV and HCV...
  9. pmc Dephosphorylation of CDK9 by protein phosphatase 2A and protein phosphatase-1 in Tat-activated HIV-1 transcription
    Tatyana Ammosova
    Center for Sickle Cell Disease, Howard University, 2121 Georgia Ave, N W Washington, DC 20059, USA
    Retrovirology 2:47. 2005
    ..In the present study we analyze relative contribution of PP2A and PP1 to dephosphorylation of CDK9 and to HIV-1 transcription in vitro and in vivo...
  10. ncbi Nuclear targeting of protein phosphatase-1 by HIV-1 Tat protein
    Tatyana Ammosova
    Center for Sickle Cell Disease, Howard University, Washington, DC 20059, USA
    J Biol Chem 280:36364-71. 2005
    ..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...
  11. ncbi HIV-1 Tat interaction with RNA polymerase II C-terminal domain (CTD) and a dynamic association with CDK2 induce CTD phosphorylation and transcription from HIV-1 promoter
    Longwen Deng
    Department of Biochemistry and Molecular Biology, George Washington University Medical Center, Washington, D C 20037, USA
    J Biol Chem 277:33922-9. 2002
    ..We suggest that CDK2 is part of a transcription complex that is required for Tat-dependent transcription and that interaction of Tat with CTD and a dynamic association of Tat with CDK2/cyclin E stimulated CTD phosphorylation by CDK2...
  12. pmc HIV-1 Tat-associated RNA polymerase C-terminal domain kinase, CDK2, phosphorylates CDK7 and stimulates Tat-mediated transcription
    Sergei Nekhai
    Department of Biochemistry and Molecular Biology, The George Washington University, School of Medicine, 2300 Eye Street N W, Washington, DC 20037, USA
    Biochem J 364:649-57. 2002
    ..They are also consistent with the observed cell-cycle-specific induction of viral gene transactivation...
  13. ncbi Nuclear protein phosphatase-1 regulates HIV-1 transcription
    Tatyana Ammosova
    Center for Sickle Cell Disease and Department of Biochemistry and Molecular Biology, Howard University, Washington, D C 20059, USA
    J Biol Chem 278:32189-94. 2003
    ..Our results indicate that PP1 might be a host cell factor that is required for HIV-1 viral transcription. Therefore, nuclear PP1 may represent a novel target for anti-HIV-1 therapeutics...
  14. pmc Phosphorylation of HIV-1 Tat by CDK2 in HIV-1 transcription
    Tatyana Ammosova
    Center for Sickle Cell Disease, Howard University College of Medicine, Washington, DC 20059, USA
    Retrovirology 3:78. 2006
    ..In the present study, we analyzed whether Tat is phosphorylated in cultured cells by CDK2 and whether Tat phosphorylation has a regulatory effect on HIV-1 transcription...
  15. pmc Expression of a protein phosphatase 1 inhibitor, cdNIPP1, increases CDK9 threonine 186 phosphorylation and inhibits HIV-1 transcription
    Tatiana Ammosova
    Center for Sickle Cell Disease, Howard University, Washington, DC 20001, USA
    J Biol Chem 286:3798-804. 2011
    ..Expression of cdNIPP1 as a part of the HIV-1 genome inhibited HIV-1 replication. Our study provides a proof-of-concept for the future development of PP1-targeting compounds as inhibitors of HIV-1 replication...
  16. pmc Hepcidin induces HIV-1 transcription inhibited by ferroportin
    Min Xu
    Center for Sickle Cell Disease, Department of Medicine, Howard University, Washington, DC 20060, USA
    Retrovirology 7:104. 2010
    ..Here, we analyzed the effect of ferroportin and hepcidin on HIV-1 transcription...
  17. pmc Iron chelators ICL670 and 311 inhibit HIV-1 transcription
    Zufan Debebe
    Center for Sickle Cell Disease, Howard University College of Medicine, Washington, DC 20060, USA
    Virology 367:324-33. 2007
    ..Further consideration should be given to the development of iron chelators for future anti-retroviral therapeutics...
  18. pmc CDK2 regulates HIV-1 transcription by phosphorylation of CDK9 on serine 90
    Denitra Breuer
    Center for Sickle Cell Disease, Department of Medicine, Howard University, 1840 7th Street, N W HURB1, Suite 202, Washington, DC 20001, USA
    Retrovirology 9:94. 2012
    ..We also found that inhibition of CDK2 by iron chelators leads to the inhibition of CDK9 activity, suggesting a functional link between CDK2 and CDK9. Here, we investigate whether CDK2 phosphorylates CDK9 and regulates its activity...
  19. pmc Regulation of HIV-1 transcription at 3% versus 21% oxygen concentration
    Sharroya Charles
    Center for Sickle Cell Disease, Howard University, Washington, DC 20001, USA
    J Cell Physiol 221:469-79. 2009
    ....
  20. pmc Chuvash polycythemia VHLR200W mutation is associated with down-regulation of hepcidin expression
    Victor R Gordeuk
    Center for Sickle Cell Disease, Department of Medicine, Howard University, Washington, DC 20060, USA
    Blood 118:5278-82. 2011
    ..In conclusion, up-regulation of the hypoxic response leads to decreased expression of hepcidin that may be independent of increased erythropoietin levels and increased RBC counts...
  21. pmc Inhibition of PP2A by LIS1 increases HIV-1 gene expression
    Nicolas Epie
    Center for Sickle Cell Disease, Howard University College of Medicine, 520 W Street N W, Washington, DC 20059, USA
    Retrovirology 3:65. 2006
    ..Previously we showed that LIS1 interacts with HIV-1 Tat protein and that this interaction was mediated by WD40 domains of LIS1. In the present study, we analyze the effect of LIS1 on Tat-mediated transcription of HIV-1 LTR...
  22. pmc HIV-1 Tat interacts with LIS1 protein
    Nicolas Epie
    Center for Sickle Cell Disease, Howard University, Washington, DC 20059, USA
    Retrovirology 2:6. 2005
    ..Tat-induced apoptosis of T-cells is attributed, in part, to the distortion of microtubules polymerization. LIS1 is a microtubule-associated protein that facilitates microtubule polymerization...
  23. ncbi A protein phosphatase from human T cells augments tat transactivation of the human immunodeficiency virus type 1 long-terminal repeat
    Diana C Bharucha
    Department of Biochemistry and Molecular Biology, The George Washington University Medical Center, Washington, DC 20037, USA
    Virology 296:6-16. 2002
    ..The results suggest a unique role of the Tat-associated phosphatase which regulates viral transcription by target-specific dephosphorylation of RNAPII during the early stages of elongation...
  24. pmc Mass spectrometry and biochemical analysis of RNA polymerase II: targeting by protein phosphatase-1
    Marina Jerebtsova
    Center for Molecular Physiology, Children s National Medical Center, Washington, DC, USA
    Mol Cell Biochem 347:79-87. 2011
    ....
  25. ncbi Protein phosphatase-1 dephosphorylates the C-terminal domain of RNA polymerase-II
    Kareem Washington
    Center for Sickle Cell Disease, Department of Biochemistry and Molecular Biology, Howard University, 2121 Georgia Avenue, Washington, D C 20059, USA
    J Biol Chem 277:40442-8. 2002
    ..Our data demonstrate that RNAPII CTD is dephosphorylated by PP1 in vitro and by PPP-type phosphatase, distinct from FCP1, in vivo...
  26. pmc Iron chelators of the di-2-pyridylketone thiosemicarbazone and 2-benzoylpyridine thiosemicarbazone series inhibit HIV-1 transcription: identification of novel cellular targets--iron, cyclin-dependent kinase (CDK) 2, and CDK9
    Zufan Debebe
    Center for Sickle Cell Disease, Department of Medicine, Howard University, Washington DC 20001, USA
    Mol Pharmacol 79:185-96. 2011
    ..Our study suggests the potential usefulness of Bp4aT or Bp4eT in antiretroviral regimens, particularly where resistance to standard treatment occurs...
  27. pmc Development of a sensitive HPLC method to measure in vitro permeability of E- and Z-isomeric forms of thiosemicarbazones in Caco-2 monolayers
    Zufan Debebe
    Center for Sickle Cell Disease, Department of Medicine, Howard University College of Medicine, Washington, DC, United States
    J Chromatogr B Analyt Technol Biomed Life Sci 906:25-32. 2012
    ..Similarly, ratios were 0.77 and 0.92 for Bp4aT, respectively. This study demonstrates that Bp4eT and Bp4aT can be efficiently transported through Caco-2 cells and can potentially be formulated for oral delivery...
  28. ncbi RNA interference directed to CDK2 inhibits HIV-1 transcription
    Tatyana Ammosova
    Center for Sickle Cell Disease, Howard University College of Medicine, NW, Washington, DC 20059, USA
    Virology 341:171-8. 2005
    ..1 cells. Our results indicate that CDK2 participates in Tat-mediated HIV-1 transcription and may serve as a potential therapeutic target...
  29. ncbi Hypoxic response contributes to altered gene expression and precapillary pulmonary hypertension in patients with sickle cell disease
    Xu Zhang
    Comprehensive Sickle Cell Center, Section of Hematology Oncology X Z, S S, V R G, Section of Cardiology A A D, and Section of Pulmonary, Critical Care, and Sleep Medicine J G N G, R F M, Department of Medicine, Institute of Human Genetics W Z, R K, Department of Pediatrics W Z, and Institute for Personalized Respiratory Medicine A A D, T A, N G C, J G N G, R F M, University of Illinois at Chicago, Chicago, IL Section of Pulmonary Critical Care, Department of Medicine, University of Chicago, Chicago, IL S F M Chuvash Republic Clinical Hospital 2, Cheboksary, Russia G M Cheboksary Children s Hospital, Cheboksary, Russia A S Center for Sickle Cell Disease, Howard University, Washington, DC T A, M X, S N Department of Medicine, Boston University School of Medicine, Boston, MA M H S, C T B Department of Biostatistics, Chile
    Circulation 129:1650-8. 2014
    ..We postulated that the hypoxic response in sickle cell disease (SCD) contributes to altered gene expression and pulmonary hypertension, a complication associated with early mortality...
  30. ncbi Identifying the membrane proteome of HIV-1 latently infected cells
    Reem Berro
    Genetics Program, Department of Biochemistry and Molecular Biology, The George Washington University, School of Medicine, Washington, DC 20037, USA
    J Biol Chem 282:8207-18. 2007
    ..This suggests that HIV-1 latently infected cells may be targeted with drugs that alter several pathways that are essential for the establishment and maintenance of latency...
  31. ncbi Potential use of pharmacological cyclin-dependent kinase inhibitors as anti-HIV therapeutics
    Anne Pumfery
    Department of Biochemistry and Molecular Biology, George Washington University, Washington, DC 20037, USA
    Curr Pharm Des 12:1949-61. 2006
    ..In this article, we will review the inhibitory mechanisms of flavopiridol and CYC202 and discuss their possible usage in AIDS treatment...
  32. pmc Ferroportin Q248h, dietary iron, and serum ferritin in community African-Americans with low to high alcohol consumption
    Victor R Gordeuk
    College of Medicine, Howard University, Washington, DC 20060, USA
    Alcohol Clin Exp Res 32:1947-53. 2008
    ..We examined the associations of ferroportin Q248H, alcohol and dietary iron with serum ferritin, aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT) concentrations in African-Americans...
  33. pmc Altered cytokine profiles in patients with Chuvash polycythemia
    Xiaomei Niu
    Center for Sickle Cell Disease and Department of Medicine, Howard University, Washington, District of Columbia 20060, USA
    Am J Hematol 84:74-8. 2009
    ..In conclusion, the up-regulated hypoxic response in Chuvash polycythemia is associated with increased plasma products of both the Th1 and Th2 pathways, but the balance between the two pathways seems to be preserved...
  34. pmc Virus-producing cells determine the host protein profiles of HIV-1 virion cores
    Steven Santos
    Department of Microbiology, Immunology and Tropical Medicine, George Washington University School of Medicine and Health Sciences, 2300 I Street NW, Ross Hall, Washington, DC 20037, USA
    Retrovirology 9:65. 2012
    ..However, the proteome of HIV-1 viral cores in the context of the type of producer cells has not yet been characterized...
  35. pmc Sickle cell disease is associated with decreased HIV but higher HBV and HCV comorbidities in U.S. hospital discharge records: a cross-sectional study
    Mehdi Nouraie
    Center for Sickle Cell Disease, Howard University, Washington, DC, USA
    Sex Transm Infect 88:528-33. 2012
    ..Some studies suggest that HIV infection progresses slowly in patients with sickle cell disease (SCD). The authors aimed to determine the relationships between SCD and HIV infection...
  36. doi Purification and characterization of aminoglycoside phosphotransferase APH(6)-Id, a streptomycin-inactivating enzyme
    Meseret Ashenafi
    Department of Biochemistry and Molecular Biology, College of Medicine, Howard University, 520 W Street, NW, Washington, DC, 20059, USA
    Mol Cell Biochem 387:207-16. 2014
    ..03 ± 0.1 mM, V(max) of 3.2 ± 1.1 μmol/min/mg, and k(cat) of 1.7 ± 0.6 s(-1). Our study demonstrates that APH(6)-Id is a bona fide streptomycin phosphotransferase, functions as a monomer, and confers resistance to streptomycin...
  37. pmc Relationship of erythropoietin, fetal hemoglobin, and hydroxyurea treatment to tricuspid regurgitation velocity in children with sickle cell disease
    Victor R Gordeuk
    Howard University, Washington, DC 20060, USA
    Blood 114:4639-44. 2009
    ..The hemolysis-lowering and hemoglobin F-augmenting effects of hydroxyurea may exert countervailing influences on pulmonary blood pressure in sickle cell disease...
  38. ncbi A128: hierarchical clustering methodology for exploration of proteomic profile in tears: seeking for markers of uveitis associated with juvenile idiopathic arthritis
    Sergei Nekhai
    Howard University, Washington, DC
    Arthritis Rheumatol 66:S168. 2014
    ..2005). Objective of the study is to reveal protein markers of JIA-associated uveitis in tears using high-resolution mass-spectrometry and hierarchical clustering methodology...
  39. pmc Iron deficiency modifies gene expression variation induced by augmented hypoxia sensing
    Xu Zhang
    Comprehensive Sickle Cell Center, Section of Hematology Oncology, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA
    Blood Cells Mol Dis 52:35-45. 2014
    ..This pattern is consistent with potentiation of HIF-1α protein stability by iron deficiency but a trend for down-regulation of HIF-2α translation by iron deficiency overriding an increase in HIF-2α protein stability. ..
  40. pmc Adenoviral E4 gene stimulates secretion of pigmental epithelium derived factor (PEDF) that maintains long-term survival of human glomerulus-derived endothelial cells
    Marina Jerebtsova
    Center for Cancer and Immunology, Children s National Medical Center, 111 Michigan Ave, N W, Washington, DC 20010, USA
    Mol Cell Proteomics 11:1378-88. 2012
    ..Thus we demonstrated that adenoviral E4 region stimulated expression and secretion of PEDF by human renal epithelial cells that acted as a survival factor for glomerulus-derived endothelial cells...
  41. ncbi Regulation of CDK9 activity by phosphorylation and dephosphorylation
    Sergei Nekhai
    Center for Sickle Cell Disease, Department of Medicine, Howard University, 520 W Street, N W Washington, DC 20059, USA
    Biomed Res Int 2014:964964. 2014
    ..We propose a novel pathway of HIV-1 transcription regulation via CDK9 Ser-90 phosphorylation by CDK2 and CDK9 Ser-175 dephosphorylation by protein phosphatase-1. ..
  42. pmc Effect of mimetic CDK9 inhibitors on HIV-1-activated transcription
    Rachel Van Duyne
    National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA 20110, USA
    J Mol Biol 425:812-29. 2013
    ..Our results suggest that it may be possible to model peptide inhibitors into available crystal structures and further find drug mimetics using in silico analysis...
  43. ncbi Cell cycle-dependent stimulation of the HIV-1 promoter by Tat-associated CAK activator
    S Nekhai
    Department of Biochemistry, George Washington University School of Medicine, Washington, DC, 20037, USA
    Virology 266:246-56. 2000
    ..The results support a mechanism whereby transactivation of the HIV promoter is regulated by cell growth signal transduction pathways that target the Tat cofactor...
  44. pmc A human primary T-lymphocyte-derived human immunodeficiency virus type 1 Tat-associated kinase phosphorylates the C-terminal domain of RNA polymerase II and induces CAK activity
    S Nekhai
    Department of Biochemistry and Molecular Biology, George Washington University School of Medicine, Washington, D C 20037, USA
    J Virol 71:7436-41. 1997
    ..Importantly, the Tat-associated kinase markedly induced CAK. We suggest that the mechanism of Tat-mediated processive transcription of the HIV-1 promoter includes a Tat-associated CAK activator...