tat gene products


Summary: Trans-acting transcription factors produced by retroviruses such as HIV. They are nuclear proteins whose expression is required for viral replication. The tat protein stimulates LONG TERMINAL REPEAT-driven RNA synthesis for both viral regulatory and viral structural proteins. tat stands for trans-activation of transcription.

Top Publications

  1. Cardarelli F, Serresi M, Bizzarri R, Giacca M, Beltram F. In vivo study of HIV-1 Tat arginine-rich motif unveils its transport properties. Mol Ther. 2007;15:1313-22 pubmed
    ..Finally, we discuss the limitations of this route in terms of acceptable cargo size. ..
  2. Ruijter J, Thygesen H, Schoneveld O, Das A, Berkhout B, Lamers W. Factor correction as a tool to eliminate between-session variation in replicate experiments: application to molecular biology and retrovirology. Retrovirology. 2006;3:2 pubmed
    ..uva.nl?subject=factor. Factor correction is an effective and efficient way to deal with between-session variation in multi-session experiments. ..
  3. D Orso I, Frankel A. Tat acetylation modulates assembly of a viral-host RNA-protein transcription complex. Proc Natl Acad Sci U S A. 2009;106:3101-6 pubmed publisher
    ..Thus, lysine acetylation can be used to modulate and evolve the strength of a viral-host RNA-protein complex, thereby tuning the levels of transcription elongation...
  4. Stewart M, Desport M, Setiyaningsih S, Hartaningsih N, Wilcox G. Analysis of Jembrana disease virus mRNA transcripts produced during acute infection demonstrates a complex transcription pattern. Virus Res. 2008;135:336-9 pubmed publisher
    ..A 67 nucleotide putative non-coding exon was identified that shared the same splice acceptor (SA) as vif and was incorporated into alternative transcripts of tat, rev and env...
  5. Sedore S, Byers S, Biglione S, Price J, Maury W, Price D. Manipulation of P-TEFb control machinery by HIV: recruitment of P-TEFb from the large form by Tat and binding of HEXIM1 to TAR. Nucleic Acids Res. 2007;35:4347-58 pubmed
    ..This suggests that in the absence of Tat, HEXIM1 may bind to TAR and repress transcription elongation of the HIV LTR. ..
  6. Mahmoudi T, Parra M, Vries R, Kauder S, Verrijzer C, Ott M, et al. The SWI/SNF chromatin-remodeling complex is a cofactor for Tat transactivation of the HIV promoter. J Biol Chem. 2006;281:19960-8 pubmed
    ..This synergism depended on the acetyltransferase activity of p300 and on Tat Lys(50) and Lys(51). In conclusion, Tat-mediated activation of the HIV promoter requires the SWI/SNF complex in synergy with the coactivator p300. ..
  7. Deng G, Qiao W, Su Y, Sha R, Geng Y, Chen Q. Internalization of Jembrana disease virus Tat: possible pathway and implication. Virus Res. 2006;121:122-33 pubmed
    ..Based on our findings, we propose that secretion and internalization of JTat may be a way for JDV to influence neighbouring cells and make the cellular environment more amenable to viral infection...
  8. Duchardt F, Fotin Mleczek M, Schwarz H, Fischer R, Brock R. A comprehensive model for the cellular uptake of cationic cell-penetrating peptides. Traffic. 2007;8:848-66 pubmed
    ..For Antp, significantly higher peptide concentrations and inhibition of endocytosis were required to induce its uptake. The relevance of these findings for import of biologically active cargos is shown. ..
  9. Ariumi Y, Serhan F, Turelli P, Telenti A, Trono D. The integrase interactor 1 (INI1) proteins facilitate Tat-mediated human immunodeficiency virus type 1 transcription. Retrovirology. 2006;3:47 pubmed
    ..These results suggest that the incoming PICs might recruit INI1 to facilitate proviral transcription. ..

More Information


  1. Barboric M, Yik J, Czudnochowski N, Yang Z, Chen R, Contreras X, et al. Tat competes with HEXIM1 to increase the active pool of P-TEFb for HIV-1 transcription. Nucleic Acids Res. 2007;35:2003-12 pubmed
    ..All these data are consistent with the model that Tat not only recruits but also increases the active pool of P-TEFb for efficient HIV-1 transcription. ..
  2. Zhang M, Drenkow J, Lankford C, Frucht D, Rabin R, Gingeras T, et al. HIV regulation of the IL-7R: a viral mechanism for enhancing HIV-1 replication in human macrophages in vitro. J Leukoc Biol. 2006;79:1328-38 pubmed
    ..The results suggest that the effects of IL-7 on HIV replication in MDM should be considered when analyzing and designing clinical trials involving treatment of patients with IL-7 or Tat vaccines. ..
  3. Kurachi S, Tashiro K, Sakurai F, Sakurai H, Kawabata K, Yayama K, et al. Fiber-modified adenovirus vectors containing the TAT peptide derived from HIV-1 in the fiber knob have efficient gene transfer activity. Gene Ther. 2007;14:1160-5 pubmed
    ..These Ad vectors should be useful for gene functional analysis and gene therapy...
  4. Gatignol A. Transcription of HIV: Tat and cellular chromatin. Adv Pharmacol. 2007;55:137-59 pubmed
  5. Al Taei S, Penning N, Simpson J, Futaki S, Takeuchi T, Nakase I, et al. Intracellular traffic and fate of protein transduction domains HIV-1 TAT peptide and octaarginine. Implications for their utilization as drug delivery vectors. Bioconjug Chem. 2006;17:90-100 pubmed
    ..Disruption of Golgi and endoplasmic reticulum dynamics was without effect on peptide localization, suggesting that endosomes and lysosomes rather than these organelles are the major acceptor compartments for these molecules. ..
  6. Apolloni A, Meredith L, Suhrbier A, Kiernan R, Harrich D. The HIV-1 Tat protein stimulates reverse transcription in vitro. Curr HIV Res. 2007;5:473-83 pubmed
    ..Together these results provide evidence that Tat can stimulate reverse transcription through an interaction with RT. ..
  7. Agbottah E, Deng L, Dannenberg L, Pumfery A, Kashanchi F. Effect of SWI/SNF chromatin remodeling complex on HIV-1 Tat activated transcription. Retrovirology. 2006;3:48 pubmed
    ..Acetylated Tat dissociates from the TAR RNA structure and recruits bromodomain-binding chromatin modifying complexes such as p/CAF and SWI/SNF to possibly facilitate transcription elongation. ..
  8. Shojania S, O Neil J. HIV-1 Tat is a natively unfolded protein: the solution conformation and dynamics of reduced HIV-1 Tat-(1-72) by NMR spectroscopy. J Biol Chem. 2006;281:8347-56 pubmed
    ..The absence of a fixed conformation and the observation of fast dynamics are consistent with the ability of Tat protein to interact with a wide variety of proteins and nucleic acid and support the concept of a natively unfolded protein...
  9. Jeeninga R, Jan B, van den Berg H, Berkhout B. Construction of doxycyline-dependent mini-HIV-1 variants for the development of a virotherapy against leukemias. Retrovirology. 2006;3:64 pubmed
    ..The therapeutic viruses use CD4 and CXCR4 for cell entry and could potentially be used against CXCR4 expressing malignancies such as T-lymphoblastic leukemia/lymphoma, NK leukemia and some myeloid leukemias. ..
  10. Epie N, Ammosova T, Turner W, Nekhai S. Inhibition of PP2A by LIS1 increases HIV-1 gene expression. Retrovirology. 2006;3:65 pubmed
    ..Our results show that inhibition of PP2A by LIS1 induces HIV-1 transcription. Our results also point to a possibility that LIS1 might function in the cells as a yet unrecognized regulatory subunit of PP2A. ..
  11. Setiyaningsih S, Desport M, Stewart M, Hartaningsih N, Wilcox G. Sequence analysis of mRNA transcripts encoding Jembrana disease virus Tat-1 in vivo. Virus Res. 2008;132:220-5 pubmed
    ..Sequence conservation in the regions of tat-1 that are critical for RNA binding and transcription activation in three different virus strains was high and the tat-2 sequences were completely conserved...
  12. Nakase I, Tadokoro A, Kawabata N, Takeuchi T, Katoh H, Hiramoto K, et al. Interaction of arginine-rich peptides with membrane-associated proteoglycans is crucial for induction of actin organization and macropinocytosis. Biochemistry. 2007;46:492-501 pubmed
    ..These data strongly suggest the possibility that the interaction of the arginine-rich peptides with the membrane-associated proteoglycans quickly activates the intracellular signals and induces actin organization and macropinocytotis. ..
  13. Chugh P, Fan S, Planelles V, Maggirwar S, Dewhurst S, Kim B. Infection of human immunodeficiency virus and intracellular viral Tat protein exert a pro-survival effect in a human microglial cell line. J Mol Biol. 2007;366:67-81 pubmed
    ..We propose that the expression of Tat may enable HIV-1 infected microglia to survive throughout the course of infection, leading to persistent HIV-1 production and infection in the central nervous system. ..
  14. Chauhan A, Tikoo A, Kapur A, Singh M. The taming of the cell penetrating domain of the HIV Tat: myths and realities. J Control Release. 2007;117:148-62 pubmed
    ..We have assembled critical information on secretory, plasma membrane penetration and transcellular properties of Tat and PTD using molecular analysis and available experimental evidences. ..
  15. Triboulet R, Mari B, Lin Y, Chable Bessia C, Bennasser Y, Lebrigand K, et al. Suppression of microRNA-silencing pathway by HIV-1 during virus replication. Science. 2007;315:1579-82 pubmed
    ..Our results highlight the involvement of the miRNA-silencing pathway in HIV-1 replication and latency. ..
  16. Berro R, Kehn K, de La Fuente C, Pumfery A, Adair R, Wade J, et al. Acetylated Tat regulates human immunodeficiency virus type 1 splicing through its interaction with the splicing regulator p32. J Virol. 2006;80:3189-204 pubmed
    ..Finally, using confocal microscopy, we found that p32 and Tat colocalize in vivo in HIV-1-infected cells. ..
  17. Ranjbar S, Rajsbaum R, Goldfeld A. Transactivator of transcription from HIV type 1 subtype E selectively inhibits TNF gene expression via interference with chromatin remodeling of the TNF locus. J Immunol. 2006;176:4182-90 pubmed
    ..Moreover, these results demonstrate a new mechanism by which the TNF gene is regulated via chromatin remodeling secondary to viral infection. ..
  18. Treand C, du Chéné I, Brès V, Kiernan R, Benarous R, Benkirane M, et al. Requirement for SWI/SNF chromatin-remodeling complex in Tat-mediated activation of the HIV-1 promoter. EMBO J. 2006;25:1690-9 pubmed
    ..These data show the requirement of Tat-mediated recruitment of SWI/SNF chromatin-remodeling complex to HIV-1 promoter in the activation of the LTR. ..
  19. White M, Gorrill T, Khalili K. Reciprocal transactivation between HIV-1 and other human viruses. Virology. 2006;352:1-13 pubmed
    ..The purpose of this review is to examine the cross-interactions between these viruses and HIV-1. ..
  20. Tunnemann G, Martin R, Haupt S, Patsch C, Edenhofer F, Cardoso M. Cargo-dependent mode of uptake and bioavailability of TAT-containing proteins and peptides in living cells. FASEB J. 2006;20:1775-84 pubmed
  21. Williams S, Chen L, Kwon H, Ruiz Jarabo C, Verdin E, Greene W. NF-kappaB p50 promotes HIV latency through HDAC recruitment and repression of transcriptional initiation. EMBO J. 2006;25:139-49 pubmed
    ..The combination of HDAC inhibitors and Tat merits consideration as a new strategy for purging latent HIV proviruses from their cellular reservoirs. ..
  22. Turner J, Ivanova G, Verbeure B, Williams D, Arzumanov A, Abes S, et al. Cell-penetrating peptide conjugates of peptide nucleic acids (PNA) as inhibitors of HIV-1 Tat-dependent trans-activation in cells. Nucleic Acids Res. 2005;33:6837-49 pubmed
    ..Endosomal or membrane release is a major factor limiting nuclear delivery and trans-activation inhibition. ..
  23. Brady J, Kashanchi F. Tat gets the "green" light on transcription initiation. Retrovirology. 2005;2:69 pubmed
    ..Finally, studies using self-cleaving ribozymes which suggested that Tat transactivation was not compatible with pausing of the RNA Pol II at the TAR site will be discussed. ..
  24. Ensoli B, Cafaro A, Caputo A, Fiorelli V, Ensoli F, Gavioli R, et al. Vaccines based on the native HIV Tat protein and on the combination of Tat and the structural HIV protein variant DeltaV2 Env. Microbes Infect. 2005;7:1392-9 pubmed
  25. Ammosova T, Jerebtsova M, Beullens M, Lesage B, Jackson A, Kashanchi F, et al. Nuclear targeting of protein phosphatase-1 by HIV-1 Tat protein. J Biol Chem. 2005;280:36364-71 pubmed
    ..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. ..
  26. Yang Z, Yik J, Chen R, He N, Jang M, Ozato K, et al. Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4. Mol Cell. 2005;19:535-45 pubmed
    ..Brd4, HEXIM1, and 7SK are all implicated in regulating cell growth, which may result from their dynamic control of the general transcription factor P-TEFb. ..
  27. Ammosova T, Berro R, Kashanchi F, Nekhai S. RNA interference directed to CDK2 inhibits HIV-1 transcription. Virology. 2005;341:171-8 pubmed
    ..1 cells. Our results indicate that CDK2 participates in Tat-mediated HIV-1 transcription and may serve as a potential therapeutic target. ..
  28. Ammosova T, Washington K, Debebe Z, Brady J, Nekhai S. Dephosphorylation of CDK9 by protein phosphatase 2A and protein phosphatase-1 in Tat-activated HIV-1 transcription. Retrovirology. 2005;2:47 pubmed
    ..Our results indicate that although PP2A dephosphorylates autophosphorylated CDK9 in vitro, in cultured cells PP1 is likely to dephosphorylate CDK9 and contribute to the regulation of activated HIV-1 transcription. ..
  29. Orii K, Grubb J, Vogler C, Levy B, Tan Y, Markova K, et al. Defining the pathway for Tat-mediated delivery of beta-glucuronidase in cultured cells and MPS VII mice. Mol Ther. 2005;12:345-52 pubmed
    ..Histology showed that GUS-Tat more efficiently reduced storage in renal tubules, retina, and bone. These studies demonstrate that Tat modification can extend the range of tissues corrected by infused enzyme. ..
  30. Desfosses Y, Solis M, Sun Q, Grandvaux N, Van Lint C, Burny A, et al. Regulation of human immunodeficiency virus type 1 gene expression by clade-specific Tat proteins. J Virol. 2005;79:9180-91 pubmed
    ..Swapping the activation domains of Tat B, C, and E identified the cyclin T1 association domain as a critical determinant of the transactivation efficiency and of Tat-defective HIV-1 provirus rescue. ..
  31. Fraldi A, Varrone F, Napolitano G, Michels A, Majello B, Bensaude O, et al. Inhibition of Tat activity by the HEXIM1 protein. Retrovirology. 2005;2:42 pubmed
    ..These results point to a pivotal role of P-TEFb for Tat's optimal transcription activity and suggest that cellular proteins that regulate P-TEFb activity might exert profound effects on Tat function in vivo. ..
  32. Deshayes S, Morris M, Divita G, Heitz F. Cell-penetrating peptides: tools for intracellular delivery of therapeutics. Cell Mol Life Sci. 2005;62:1839-49 pubmed
    ..Here, we give an extensive review of peptide-mediated delivery systems and discuss their applications, with particular focus on the mechanisms leading to cellular internalization. ..
  33. Calabro V, Daugherty M, Frankel A. A single intermolecular contact mediates intramolecular stabilization of both RNA and protein. Proc Natl Acad Sci U S A. 2005;102:6849-54 pubmed
    ..In addition, the bound structure of BIV TAR in the chameleon peptide complex is strikingly similar to the bound conformation of HIV TAR, suggesting new strategies for the development of HIV TAR binding molecules...
  34. Bettaccini A, Baj A, Accolla R, Basolo F, Toniolo A. Proliferative activity of extracellular HIV-1 Tat protein in human epithelial cells: expression profile of pathogenetically relevant genes. BMC Microbiol. 2005;5:20 pubmed
    ..These effects may favor virus replication and may facilitate the mother-to-child transmission of virus. ..
  35. Albarran B, To R, Stayton P. A TAT-streptavidin fusion protein directs uptake of biotinylated cargo into mammalian cells. Protein Eng Des Sel. 2005;18:147-52 pubmed
    ..Taken together, these results demonstrate that TAT-SA can be used to direct intracellular delivery of large biotinylated cargo to intracellular compartments and that biotinylated PPAA can direct cytoplasmic delivery where desired. ..
  36. Schulte A, Czudnochowski N, Barboric M, Schönichen A, Blazek D, Peterlin B, et al. Identification of a cyclin T-binding domain in Hexim1 and biochemical analysis of its binding competition with HIV-1 Tat. J Biol Chem. 2005;280:24968-77 pubmed
    ..Our data suggest a model where HIV-1 Tat competes with Hexim1 for cyclin T1 binding, thus releasing P-TEFb from the inactive complex to stimulate the transcription of HIV-1 gene expression. ..
  37. Bennasser Y, LE S, Benkirane M, Jeang K. Evidence that HIV-1 encodes an siRNA and a suppressor of RNA silencing. Immunity. 2005;22:607-19 pubmed
    ..Tat abrogates the cell's RNA-silencing defense by subverting the ability of Dicer to process precursor double-stranded RNAs into siRNAs. ..
  38. Brès V, Gomes N, Pickle L, Jones K. A human splicing factor, SKIP, associates with P-TEFb and enhances transcription elongation by HIV-1 Tat. Genes Dev. 2005;19:1211-26 pubmed
    ..These findings suggest that SKIP plays independent roles in transcription elongation and pre-mRNA splicing. ..
  39. Olsen G, Edwards T, Deka P, Varani G, Sigurdsson S, Drobny G. Monitoring tat peptide binding to TAR RNA by solid-state 31P-19F REDOR NMR. Nucleic Acids Res. 2005;33:3447-54 pubmed
    ..To our knowledge, these experiments provide the first example of a solid-state NMR distance measurement in an RNA-peptide complex. ..
  40. Hetzer C, Dormeyer W, Schnolzer M, Ott M. Decoding Tat: the biology of HIV Tat posttranslational modifications. Microbes Infect. 2005;7:1364-9 pubmed
    ..Tat undergoes multiple posttranslational modifications that regulate the dynamics and complexity of these interactions. The biology of these modifications and their role in Tat function are reviewed. ..
  41. Mondal D, Williams C, Ali M, Eilers M, Agrawal K. The HIV-1 Tat protein selectively enhances CXCR4 and inhibits CCR5 expression in megakaryocytic K562 cells. Exp Biol Med (Maywood). 2005;230:631-44 pubmed
    ..Because megakaryocytes may play a crucial role in HIV-1 infectivity in viral reservoirs, our findings implicate a role for Tat protein in dictating co-receptor usage in lineage-committed HPCs. ..
  42. Liang X, Casimiro D, Schleif W, Wang F, Davies M, Zhang Z, et al. Vectored Gag and Env but not Tat show efficacy against simian-human immunodeficiency virus 89.6P challenge in Mamu-A*01-negative rhesus monkeys. J Virol. 2005;79:12321-31 pubmed
    ..The implications of these results in the development of an HIV-1 vaccine will be discussed. ..
  43. Shiraishi T, Pankratova S, Nielsen P. Calcium ions effectively enhance the effect of antisense peptide nucleic acids conjugated to cationic tat and oligoarginine peptides. Chem Biol. 2005;12:923-9 pubmed
    ..The present results show that Ca(2+) can be used as an effective enhancer for in vitro cellular delivery of cationic peptide-conjugated PNA oligomers, and also emphasize the significance of the endosomal escape route for such peptides. ..
  44. Tripathi S, Chaubey B, Ganguly S, Harris D, Casale R, Pandey V. Anti-HIV-1 activity of anti-TAR polyamide nucleic acid conjugated with various membrane transducing peptides. Nucleic Acids Res. 2005;33:4345-56 pubmed
    ..8 microM). These results indicate that anti-HIV-1 PNA conjugated with MTD peptides are not only inhibitory to HIV-1 replication in vitro but are also potent virucidal agents which render HIV-1 virions non-infectious upon brief exposure. ..
  45. Guillon C, Stankovic K, Ataman Onal Y, Biron F, Verrier B. Evidence for CTL-mediated selection of Tat and Rev mutants after the onset of the asymptomatic period during HIV type 1 infection. AIDS Res Hum Retroviruses. 2006;22:1283-92 pubmed
    ..CTL-mediated selection appears to be an important determinant of HIV-1 regulatory gene sequence evolution during the early stages of infection. ..
  46. Nagel F, Falkenburger B, Tönges L, Kowsky S, Pöppelmeyer C, Schulz J, et al. Tat-Hsp70 protects dopaminergic neurons in midbrain cultures and in the substantia nigra in models of Parkinson's disease. J Neurochem. 2008;105:853-64 pubmed publisher
    ..The use of Tat-fusion proteins might therefore be a valuable tool to deliver molecular chaperones like Hsp70 into the brain and may be the starting point for new protective strategies in neurodegenerative diseases. ..
  47. Hayashi K, Pu H, Andras I, Eum S, Yamauchi A, Hennig B, et al. HIV-TAT protein upregulates expression of multidrug resistance protein 1 in the blood-brain barrier. J Cereb Blood Flow Metab. 2006;26:1052-65 pubmed
    ..These results indicate that Tat exposure can lead to alterations of the BBB functions and decrease HAART efficacy in the CNS through overexpression of drug efflux transporters. ..
  48. Sagan S, Burlina F, Delaroche D, Aussedat B, Aubry S, Bolbach G, et al. [Tracking Trojan peptides in cells]. J Soc Biol. 2006;200:213-9 pubmed
    ..Therefore, we have developed a MALDI-TOF mass spectrometry-based quantification method to track these peptides inside cells. This new method is presented in this review. ..
  49. Marquez N, Sancho R, Macho A, Moure A, Masip I, Messeguer A, et al. Anti-Tat and anti-HIV activities of trimers of n-alkylglycines. Biochem Pharmacol. 2006;71:596-604 pubmed
    ..Likewise, the structural simplicity of N-alkylglycine oligomers makes these peptidomimetics amenable to structural manipulation, thus facilitating the optimisation of lead molecules for drug-like properties. ..
  50. Renigunta A, Krasteva G, Konig P, Rose F, Klepetko W, Grimminger F, et al. DNA transfer into human lung cells is improved with Tat-RGD peptide by caveoli-mediated endocytosis. Bioconjug Chem. 2006;17:327-34 pubmed
    ..The enhancement of DNA uptake by Tat-RGD is suggested to be mediated by caveoli-dependent endocytosis. ..
  51. Ammosova T, Berro R, Jerebtsova M, Jackson A, Charles S, Klase Z, et al. Phosphorylation of HIV-1 Tat by CDK2 in HIV-1 transcription. Retrovirology. 2006;3:78 pubmed
    ..Our results indicate for the first time that Tat is phosphorylated in vivo; Tat phosphorylation is likely to be mediated by CDK2; and phosphorylation of Tat is important for HIV-1 transcription. ..
  52. Maeda K, Kanno H, Yamazaki Y, Kubo A, Sato F, Yamaguchi Y, et al. Transplantation of Von Hippel-Lindau peptide delivered neural stem cells promotes recovery in the injured rat spinal cord. Neuroreport. 2009;20:1559-63 pubmed publisher
    ..Thus, our finding of the neuronal differentiation through VHL-peptide transfer has the great potential to cure the spinal cord injury. ..
  53. Patsch C, Peitz M, Otte D, Kesseler D, Jungverdorben J, Wunderlich F, et al. Engineering cell-permeant FLP recombinase for tightly controlled inducible and reversible overexpression in embryonic stem cells. Stem Cells. 2010;28:894-902 pubmed publisher
    ..We expect our FLP transduction system to become widely useful for numerous genetic interventions addressing complex biological questions and the generation of transgene-free therapeutically applicable ES cell-derived cells. ..