Biopolym. Cell. 2015; 31(2):154-158.
http://dx.doi.org/10.7124/bc.0008DB
Short Communications
The accumulation of the basic domain of HIV-1 Tat protein in the nuclei and the nucleoli is different from the accumulation of full-length Tat proteins
1, 2Musinova Y. R., 1, 2Sheval E. V.
  1. A. N. Belozersky Institute of Physico-Chemical Biology, M. V. Lomonosov Moscow State University
    Leninskie gory, house 1, building 40, Moscow, Russian Federation, 119992
  2. LIA 1066 French-Russian Joint Cancer Research Laboratory
    Villejuif, France–Moscow, Russian Federation

Abstract

Aim. Protein fragments coding for nuclear (NLS) and/or nucleolar (NoLS) localization signals are often used for the investigation of the mechanisms of protein accumulation inside the nuclei and the nucleoli, but it is possible that accumulation mechanisms in full-length proteins will be different. Methods. Here, we compared the nuclear and nucleolar accumulation of HIV-1 Tat protein and its basic domain containing both NLS and NoLS. Results. The pattern of accumulation of the basic domain of HIV-1 Tat protein in the nuclei and the nucleoli is different from that of full-length Tat proteins: the basic domain is accumulated weaker inside the nuclei, but stronger in the nucleoli as compared to the full-length protein. Conclusion. The molecular mechanism of nuclear and nucleolar accumulation of full-length Tat protein might be different from that of the Tat protein fragments.
Keywords: nucleus, nucleolus, NLS, NoLS, HIV-1 Tat
Full text: (PDF, in English)

References

[1] Van Lint C, Bouchat S, Marcello A. HIV-1 transcription and latency: an update. Retrovirology. 2013;10:67.
[2] Mbonye U, Karn J. Transcriptional control of HIV latency: cellular signaling pathways, epigenetics, happenstance and the hope for a cure. Virology. 2014;454-455:328-39.
[3] Romani B, Engelbrecht S, Glashoff RH. Functions of Tat: the versatile protein of human immunodeficiency virus type 1. J Gen Virol. 2010;91(Pt 1):1-12.
[4] Kuppuswamy M, Subramanian T, Srinivasan A, Chinnadurai G. Multiple functional domains of Tat, the trans-activator of HIV-1, defined by mutational analysis. Nucleic Acids Res. 1989;17(9):3551-61.
[5] Ruben S, Perkins A, Purcell R, Joung K, Sia R, Burghoff R, Haseltine WA, Rosen CA. Structural and functional characterization of human immunodeficiency virus tat protein. J Virol. 1989;63(1):1-8.
[6] Coiras M, Camafeita E, Ure?a T, L?pez JA, Caballero F, Fern?ndez B, L?pez-Huertas MR, P?rez-Olmeda M, Alcam? J. Modifications in the human T cell proteome induced by intracellular HIV-1 Tat protein expression. Proteomics. 2006; 6(Suppl 1):S63–73.
[7] Stauber RH, Pavlakis GN. Intracellular trafficking and interactions of the HIV-1 Tat protein. Virology. 1998;252(1):126-36.
[8] Dundr M. Nuclear bodies: multifunctional companions of the genome. Curr Opin Cell Biol. 2012;24(3):415-22.
[9] Lange A, Mills RE, Lange CJ, Stewart M, Devine SE, Corbett AH. Classical nuclear localization signals: definition, function, and interaction with importin alpha. J Biol Chem. 2007;282(8):5101-5.
[10] Emmott E, Hiscox JA. Nucleolar targeting: the hub of the matter. EMBO Rep. 2009;10(3):231-8.
[11] Rhim H, Echetebu CO, Herrmann CH, Rice AP. Wild-type and mutant HIV-1 and HIV-2 Tat proteins expressed in Escherichia coli as fusions with glutathione S-transferase. J Acquir Immune Defic Syndr. 1994;7(11):1116-21.
[12] Musinova YR, Lisitsyna OM, Golyshev SA, Tuzhikov AI, Polyakov VY, Sheval EV. Nucleolar localization/retention signal is responsible for transient accumulation of histone H2B in the nucleolus through electrostatic interactions. Biochim Biophys Acta. 2011;1813(1):27-38.
[13] Hauber J, Malim MH, Cullen BR. Mutational analysis of the conserved basic domain of human immunodeficiency virus tat protein. J Virol. 1989;63(3):1181-7.
[14] Meredith LW, Sivakumaran H, Major L, Suhrbier A, Harrich D. Potent inhibition of HIV-1 replication by a Tat mutant. PLoS One. 2009;4(11):e7769.
[15] Li YP. Protein B23 is an important human factor for the nucleolar localization of the human immunodeficiency virus protein Tat. J Virol. 1997;71(5):4098-102.
[16] Orsini MJ, Debouck CM. Inhibition of human immunodeficiency virus type 1 and type 2 Tat function by transdominant Tat protein localized to both the nucleus and cytoplasm. J Virol. 1996;70(11):8055-63.
[17] Pearson L, Garcia J, Wu F, Modesti N, Nelson J, Gaynor R. A transdominant tat mutant that inhibits tat-induced gene expression from the human immunodeficiency virus long terminal repeat. Proc Natl Acad Sci U S A. 1990;87(13):5079-83.
[18] Cardarelli F, Serresi M, Albanese A, Bizzarri R, Beltram F. Quantitative analysis of Tat peptide binding to import carriers reveals unconventional nuclear transport properties. J Biol Chem. 2011;286(14):12292-9.
[19] Musinova YR, Kananykhina EY, Potashnikova DM, Lisitsyna OM, Sheval EV. A charge-dependent mechanism is responsible for the dynamic accumulation of proteins inside nucleoli. Biochim Biophys Acta. 2015;1853(1):101-10.