A tripartite DNA-binding element, comprised of the nuclear localization signal and two AT-hook motifs, mediates the association of LEDGF/p75 with chromatin in vivo
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Lens epithelium-derived growth factor p75 (LEDGF/p75) is a DNA-binding, transcriptional co-activator that participates in HIV-1 integration site targeting. Using complementary approaches, we determined the mechanisms of LEDGF/p75 DNA-binding in vitro and chromatin-association in living cells. The binding of highly-purified, recombinant protein was assayed by surface plasmon resonance (SPR) and electrophoretic mobility gel shift. Neither assay revealed evidence for sequence-specific DNA-binding. Residues 146-197 spanning the nuclear localization signal (NLS) and two AT-hook motifs mediated non-specific DNA-binding, and DNA-binding deficient mutants retained the ability to efficiently stimulate HIV-1 integrase activity in vitro. Chromatin-association was assessed by visualizing the localization of EGFP fusion proteins in interphase and mitotic cells. Although a conserved N-terminal PWWP domain was not required for binding to condensed mitotic chromosomes, its deletion subtly affected the nucleoplasmic distribution of the protein during interphase. A dual AT-hook mutant associated normally with chromatin, yet when the mutations were combined with NLS changes or deletion of the PWWP domain, chromatin-binding function was lost. As the PWWP domain did not readily bind free DNA in vitro, our results indicate that chromatin-association is primarily affected through DNA-binding, with the PWWP domain likely contributing a protein interaction to the overall affinity of LEDGF/p75 for human chromatin.
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The N-terminal half of LEDGF/p75 contains a PWWP chromatin reader domain and two AT-hook DNA-binding motifs that mediate chromatin association, while its C-terminal IBD binds integrase.
“Elements including a PWWP chromatin reader domain and two copies of an AT-hook DNA binding motif in the N-terminal half of the protein mediate its association with chromatin, while the C-terminal IN-binding domain (IBD) confers binding to IN103–105.”
From Structure and function of retroviral integrase (2022) · cites this paper as [104]
LEDGF/p75 acts as a bimodal tether in lentiviral integration targeting.
“LEDGF/p75 appears to function as a bimodal tether in lentiviral integration targeting.”
From Structure and function of retroviral integrase (2022) · cites this paper as [104]
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[31] PHD: Predicting one-dimensional protein structure by profile-based neural networks
Rost, B. (1996) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(96)66033-9 · Cited by 1,282 · see citing works
SMART 4.0: towards genomic data integration
Letunić, I. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkh088 · Cited by 997 · see citing works
HIV-1 Integrase Forms Stable Tetramers and Associates with LEDGF/p75 Protein in Human Cells
Cherepanov, P., Maertens, G., Proost, P., Devreese, B., Van Beeumen, J., Engelborghs, Y., De Clercq, E., & Debyser, Z. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209278200 · Cited by 704 · see citing works
Finding nuclear localization signals
Cokol, M., Nair, R. P., & Rost, B. (2000) · EMBO Reports · doi:10.1093/embo-reports/kvd092 · Cited by 692 · see citing works
A role for LEDGF/p75 in targeting HIV DNA integration
Ciuffi, A., Llano, M., Poeschla, E., Hoffmann, C., Leipzig, J., Shinn, P., Ecker, J. R., & Bushman, F. (2005) · Nature Medicine · doi:10.1038/nm1329 · Cited by 658 · see citing works
Molecular biology of HMGA proteins: hubs of nuclear function
Reeves, R. (2001) · Gene · doi:10.1016/s0378-1119(01)00689-8 · Cited by 535 · see citing works
Binding and Stimulation of HIV-1 Integrase by a Human Homolog of Yeast Transcription Factor SNF5
Kalpana, G. V., Marmon, S., Wang, W., Crabtree, G. R., & Goff, S. P. (1994) · Science · doi:10.1126/science.7801128 · Cited by 530 · see citing works
Comparison of ARM and HEAT protein repeats
Andrade-Navarro, M. A., Petosa, C., O’Donoghue, S. I., Müller, C. W., & Peer Bork, B. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.4624 · Cited by 507 · see citing works
AT-hook motifs identified in a wide variety of DNA-binding proteins
Aravind, L. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.19.4413 · Cited by 498 · see citing works
LEDGF/p75 Is Essential for Nuclear and Chromosomal Targeting of HIV-1 Integrase in Human Cells
Maertens, G., Cherepanov, P., Pluymers, W., Busschots, K., De Clercq, E., Debyser, Z., & Engelborghs, Y. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303594200 · Cited by 493 · see citing works
Structural basis for the recognition between HIV-1 integrase and transcriptional coactivator p75
Cherepanov, P., Ambrosio, A. L. B., Rahman, S., Ellenberger, T., & Engelman, A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506924102 · Cited by 408 · see citing works
Huth, J. R., Bewley, C. A., Nissen, M. S., Evans, J. N. S., Reeves, R., Gronenborn, A. M., & Clore, G. M. (1997) · Nature Structural Biology · doi:10.1038/nsb0897-657 · Cited by 404 · see citing works
Biological control through regulated transcriptional coactivators
Spiegelman, B. M., & Heinrich, R. (2004) · Cell · doi:10.1016/j.cell.2004.09.037 · Cited by 377 · see citing works
Farnet, C. M., & Bushman, F. D. (1997) · Cell · doi:10.1016/s0092-8674(00)81888-7 · Cited by 358 · see citing works
Llano, M., Vanegas, M., Fregoso, O., Saenz, D., Chung, S., Peretz, M., & Poeschla, E. M. (2004) · Journal of Virology · doi:10.1128/jvi.78.17.9524-9537.2004 · Cited by 305 · see citing works
Ge, H., Si, Y., & Roeder, R. G. (1998) · The EMBO Journal · doi:10.1093/emboj/17.22.6723 · Cited by 289 · see citing works
Cherepanov, P., Devroe, E., Silver, P. A., & Engelman, A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406307200 · Cited by 287 · see citing works
A previously unidentified host protein protects retroviral DNA from autointegration
Lee, M. S., & Craigie, R. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.4.1528 · Cited by 281 · see citing works
Dorfman, T., Luban, J., Goff, S. P., Haseltine, W. A., & Göttlinger, H. G. (1993) · Journal of Virology · doi:10.1128/jvi.67.10.6159-6169.1993 · Cited by 279 · see citing works
Chen, T., Tsujimoto, N., & Li, E. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.20.9048-9058.2004 · Cited by 273 · see citing works
The PWWP domain of mammalian DNA methyltransferase Dnmt3b defines a new family of DNA-binding folds
Qiu, C., Sawada, K., Zhang, X., & Cheng, X. (2002) · Nature Structural Biology · doi:10.1038/nsb759 · Cited by 261 · see citing works
Emiliani, S., Mousnier, A., Busschots, K., Maroun, M., Maele, B. V., Tempé, D., Vandekerckhove, L., Moisant, F., Benslama, L., Witvrouw, M., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501378200 · Cited by 243 · see citing works
Solution structure of the HIV-1 integrase-binding domain in LEDGF/p75
Cherepanov, P., Sun, Z.-Y. J., Rahman, S., Maertens, G., Wagner, G., & Engelman, A. (2005) · Nature Structural & Molecular Biology · doi:10.1038/nsmb937 · Cited by 235 · see citing works
Stec, I., Nagl, S., van Ommen, G. B., & den Dunnen, J. T. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01449-6 · Cited by 214 · see citing works
Nuclear localization signals overlap DNA- or RNA-binding domains in nucleic acid-binding proteins
LaCasse, E. C., & Lefebvre, Y. A. (1995) · Nucleic Acids Research · doi:10.1093/nar/23.10.1647 · Cited by 210 · see citing works
The Interaction of LEDGF/p75 with Integrase Is Lentivirus-specific and Promotes DNA Binding
Busschots, K., Vercammen, J., Emiliani, S., Benarous, R., Engelborghs, Y., Christ, F., & Debyser, Z. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m411681200 · Cited by 208 · see citing works
Chromatin Targeting of de Novo DNA Methyltransferases by the PWWP Domain
Ge, Y., Pu, M., Gowher, H., Wu, H., Ding, J., Jeltsch, A., & Xu, G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312296200 · Cited by 206 · see citing works
Loopy Proteins Appear Conserved in Evolution
Liu, J., Tan, H., & Rost, B. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00736-2 · Cited by 189 · see citing works
Vanegas, M., Llano, M., Delgado, S., Thompson, D., Peretz, M., & Poeschla, E. M. (2005) · Journal of Cell Science · doi:10.1242/jcs.02299 · Cited by 172 · see citing works
LEDGF, a survival factor, activates stress-related genes
Shinohara, T., Singh, D. P., & Fatma, N. (2002) · Progress in Retinal and Eye Research · doi:10.1016/s1350-9462(02)00007-1 · Cited by 172 · see citing works
Human cell proteins and human immunodeficiency virus DNA integration
Turlure, F. (2004) · Frontiers in bioscience · doi:10.2741/1472 · Cited by 156 · see citing works
Self-citationBIACORE: an affinity biosensor system for characterization of biomolecular interactions
Malmqvist, M. (1999) · Biochemical Society Transactions · doi:10.1042/bst0270335 · Cited by 151 · see citing works
Fatma, N., Singh, D. P., Shinohara, T., & Chylack, L. T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100733200 · Cited by 134 · see citing works
Daniels‐Wells, T. R., Zhang, J., Gutierrez, I., Elliot, M. L., Yamada, B. S., Heeb, M. J., Sheets, S. M., Wu, X., & Casiano, C. A. (2004) · The Prostate · doi:10.1002/pros.20112 · Cited by 130 · see citing works
Singh, D. P., Fatma, N., Kimura, A., Chylack, L. T., & Shinohara, T. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.4887 · Cited by 126 · see citing works
Izumoto, Y., Kuroda, T., Harada, H., Kishimoto, T., & Nakamura, H. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.7233 · Cited by 125 · see citing works
Hindmarsh, P. L., Ridky, T. W., Reeves, R., Andrake, M., Skalka, A. M., & Leis, J. P. (1999) · Journal of Virology · doi:10.1128/jvi.73.4.2994-3003.1999 · Cited by 119 · see citing works
Trichostatin and Leptomycin: Inhibition of Histone Deacetylation and Signal‐Dependent Nuclear Export
Yoshida, M., & Horinouchi, S. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb09397.x · Cited by 116 · see citing works
Maertens, G. N., Cherepanov, P., Debyser, Z., Engelborghs, Y., & Engelman, A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404700200 · Cited by 110 · see citing works
Vandegraaff, N., Devroe, E., Turlure, F., Silver, P. A., & Engelman, A. (2005) · Virology · doi:10.1016/j.virol.2005.11.022 · Cited by 106 · see citing works
Self-citationGanapathy, V., & Casiano, C. A. (2004) · Arthritis & Rheumatism · doi:10.1002/art.20095 · Cited by 99 · see citing works
Ahuja, H. G., Hong, J., Aplan, P. D., Tcheurekdjian, L., Forman, S. J., & Slovak, M. L. (2000) · PubMed · Cited by 97 · see citing works
Retroviral cDNA Integration: Stimulation by HMG I Family Proteins
Li, L., Yoder, K. E., Hansen, M. S., Olvera, J., Miller, M. D., & Bushman, F. D. (2000) · Journal of Virology · doi:10.1128/jvi.74.23.10965-10974.2000 · Cited by 90 · see citing works
BIACORE J: a new platform for routine biomolecular interaction analysis†
Rich, R. L., & Myszka, D. G. (2001) · Journal of Molecular Recognition · doi:10.1002/jmr.535 · Cited by 80 · see citing works
Nishizawa, Y., Usukura, J., Singh, D. P., Chylack, L. T., & Shinohara, T. (2001) · Cell and Tissue Research · doi:10.1007/s004410100398 · Cited by 77 · see citing works
Wu, X., Daniels‐Wells, T. R., Molinaro, C., Lilly, M. B., & Casiano, C. A. (2002) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401063 · Cited by 77 · see citing works
Harris, D., & Engelman, A. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m002626200 · Cited by 71 · see citing works
Singh, D. P., Kubo, E., Takamura, Y., Shinohara, T., Kumar, A., Chylack, L. T., & Fatma, N. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.10.054 · Cited by 67 · see citing works
Mansharamani, M., Graham, D. R. M., Monie, D., Lee, K. K., Hildreth, J. E. K., Siliciano, R. F., & Wilson, K. L. (2003) · Journal of Virology · doi:10.1128/jvi.77.24.13084-13092.2003 · Cited by 55 · see citing works
Hussey, D. J., Moore, S., Nicola, M., & Dobrovic, A. (2001) · BMC Genetics · doi:10.1186/1471-2156-2-20 · Cited by 48 · see citing works
Activity of recombinant HIV-1 integrase on mini-HIV DNA
Cherepanov, P., Surratt, D., Toelen, J., Pluymers, W., Griffith, J. D., Clercq, E. D., & Debyser, Z. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.10.2202 · Cited by 47 · see citing works
The Roles of Cellular Factors in Retroviral Integration
Engelman, A. (2003) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-19012-4_6 · Cited by 45 · see citing works
NUP98-LEDGF fusion and t(9;11) in transformed chronic myeloid leukemia
Grand, F., Koduru, P. R. K., Cross, N. C. P., & Allen, S. L. (2005) · Leukemia Research · doi:10.1016/j.leukres.2005.05.002 · Cited by 36 · see citing works
Bradley, C. M., & Craigie, R. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509078102 · Cited by 12 · see citing works
The terminal nucleotide of the Mu genome controls catalysis of DNA strand transfer
Goldhaber-Gordon, I., Early, M. H., & Baker, T. A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0832468100 · Cited by 10 · see citing works
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Simon, V. R., Ho, D. D., & Karim, Q. A. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69157-5 · Cited by 730 · see citing works
Survey of the year 2003 commercial optical biosensor literature
Rich, R. L., & Myszka, D. G. (2004) · Journal of Molecular Recognition · doi:10.1002/jmr.726 · Cited by 505 · see citing works
Shun, M.-C., Raghavendra, N. K., Vandegraaff, N., Daigle, J. E., Hughes, S., Kellam, P., Cherepanov, P., & Engelman, A. (2007) · Genes & Development · doi:10.1101/gad.1565107 · Cited by 467 · see citing works
Craigie, R., & Bushman, F. D. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006890 · Cited by 327 · see citing works
The road to chromatin — nuclear entry of retroviruses
Suzuki, Y., & Craigie, R. (2007) · Nature Reviews Microbiology · doi:10.1038/nrmicro1579 · Cited by 287 · see citing works
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Marshall, H. M., Ronen, K., Berry, C., Llano, M., Sutherland, H., Saenz, D., Bickmore, W., Poeschla, E., & Bushman, F. D. (2007) · PLoS ONE · doi:10.1371/journal.pone.0001340 · Cited by 241 · see citing works
Lesbats, P., Engelman, A., & Cherepanov, P. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.6b00125 · Cited by 232 · see citing works
The lentiviral integrase binding protein LEDGF/p75 and HIV-1 replication
Engelman, A., & Cherepanov, P. (2008) · PLoS Pathogens · doi:10.1371/journal.ppat.1000046 · Cited by 231 · see citing works
Structural basis for high-affinity binding of LEDGF PWWP to mononucleosomes
Eidahl, J. O., Crowe, B. L., North, J. A., McKee, C. J., Shkriabai, N., Feng, L., Plumb, M., Graham, R. L., Gorelick, R. J., Hess, S., et al. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt074 · Cited by 207 · see citing works
Multimode, Cooperative Mechanism of Action of Allosteric HIV-1 Integrase Inhibitors*
Kessl, J., Jena, N., Koh, Y., Taskent-Sezgin, H., Slaughter, A., Feng, L., de Silva, S., Wu, L., Grice, S. L., Engelman, A., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.354373 · Cited by 189 · see citing works
Inhibiting HIV-1 integrase by shifting its oligomerization equilibrium
Hayouka, Z., Rosenbluh, J., Levin, A., Loya, S., Lebendiker, M., Veprintsev, D. B., Kotler, M., Hizi, A., Loyter, A., & Friedler, A. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0700781104 · Cited by 181 · see citing works
Cherepanov, P. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkl885 · Cited by 173 · see citing works
van Nuland, R., van Schaik, F. M. A., Simonis, M., van Heesch, S., Cuppen, E. P. J. G., Boelens, R., Timmers, H. T. M., & van Ingen, H. (2013) · Epigenetics & Chromatin · doi:10.1186/1756-8935-6-12 · Cited by 168 · see citing works
Hare, S., Shun, M.-C., Gupta, S. S., Valkov, E., Engelman, A., & Cherepanov, P. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000259 · Cited by 166 · see citing works
Rijck, J. D., Vandekerckhove, L., Gijsbers, R., Hombrouck, A., Hendrix, J., Vercammen, J., Engelborghs, Y., Christ, F., & Debyser, Z. (2006) · Journal of Virology · doi:10.1128/jvi.00801-06 · Cited by 165 · see citing works
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Ferris, A. L., Wu, X., Hughes, C. M., Stewart, C., Smith, S. J., Milne, T. A., Wang, G. G., Shun, M.-C., Allis, C. D., Engelman, A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914142107 · Cited by 141 · see citing works
Molecular mechanisms of retroviral integration site selection
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Atkins, J. F., & Björk, G. R. (2009) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00010-08 · Cited by 136 · see citing works
Schrijvers, R., Rijck, J. D., Demeulemeester, J., Adachi, N., Vets, S., Ronen, K., Christ, F., Bushman, F. D., Debyser, Z., & Gijsbers, R. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002558 · Cited by 135 · see citing works
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McKee, C. J., Kessl, J. J., Shkriabai, N., Dar, M. J., Engelman, A., & Kvaratskhelia, M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m805843200 · Cited by 128 · see citing works
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Balakrishnan, M., Yant, S. R., Tsai, L., O’Sullivan, C., Bam, R. A., Tsai, A., Niedziela-Majka, A., Stray, K. M., Sakowicz, R., & Cihlar, T. (2013) · PLoS ONE · doi:10.1371/journal.pone.0074163 · Cited by 126 · see citing works
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Survey of the year 2006 commercial optical biosensor literature
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Ochs, R., Mähler, M., Basu, A., Ríos-Colón, L., Sanchez, T. W., Andrade, L. E. C., Fritzler, M. J., & Casiano, C. A. (2015) · Clinical and Experimental Medicine · doi:10.1007/s10238-015-0367-0 · Cited by 98 · see citing works
DNA bar coding and pyrosequencing to analyze adverse events in therapeutic gene transfer
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Wang, H., Jurado, K. A., Wu, X., Shun, M.-C., Li, X., Ferris, A. L., Smith, S. J., Patel, P. A., Fuchs, J. R., Cherepanov, P., et al. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks913 · Cited by 97 · see citing works
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Bartholomeeusen, K., Rijck, J. D., Busschots, K., Desender, L., Gijsbers, R., Emiliani, S., Bénarous, R., Debyser, Z., & Christ, F. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.06.090 · Cited by 87 · see citing works
Allosteric Inhibition of Human Immunodeficiency Virus Integrase
Gupta, K., Brady, T., Dyer, B. M., Malani, N., Hwang, Y., Male, F., Nolte, R. T., Wang, L., Velthuisen, E., Jeffrey, J., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.551119 · Cited by 81 · see citing works
Piecing together the structure of retroviral integrase, an important target in AIDS therapy
Jaskólski, M., Alexandratos, J. N., Bujacz, G., & Wlodawer, A. (2009) · FEBS Journal · doi:10.1111/j.1742-4658.2009.07009.x · Cited by 83 · see citing works
Interactions between Retroviruses and the Host Cell Genome
Poletti, V., & Mavilio, F. (2017) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2017.10.001 · Cited by 81 · see citing works
The Molecular Biology of HIV Integrase
Craigie, R. (2012) · Future Virology · doi:10.2217/fvl.12.56 · Cited by 82 · see citing works
Shun, M.-C., Botbol, Y., Li, X., Di Nunzio, F., Daigle, J. E., Yan, N., Lieberman, J., Lavigne, M., & Engelman, A. (2008) · Journal of Virology · doi:10.1128/jvi.01561-08 · Cited by 78 · see citing works
p12 Tethers the Murine Leukemia Virus Pre-integration Complex to Mitotic Chromosomes
Elis, E., Ehrlich, M., Prizan-Ravid, A., Laham-Karam, N., & Bacharach, E. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1003103 · Cited by 76 · see citing works
Multifaceted HIV integrase functionalities and therapeutic strategies for their inhibition
Engelman, A. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.rev119.006901 · Cited by 78 · see citing works
High-resolution profiling of the LEDGF/p75 chromatin interaction in the ENCODE region
Rijck, J. D., Bartholomeeusen, K., Ceulemans, H., Debyser, Z., & Gijsbers, R. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq410 · Cited by 74 · see citing works
Chromatin organization and virus gene expression
Lieberman, P. M. (2008) · Journal of Cellular Physiology · doi:10.1002/jcp.21421 · Cited by 77 · see citing works
Multiple cellular proteins interact with LEDGF/p75 through a conserved unstructured consensus motif
Tesina, P., Čermáková, K., Hořejší, M., Procházková, K., Fábry, M., Sharma, S., Christ, F., Demeulemeester, J., Debyser, Z., Rijck, J. D., et al. (2015) · Nature Communications · doi:10.1038/ncomms8968 · Cited by 74 · see citing works
Integration Site Selection by Retroviral Vectors: Molecular Mechanism and Clinical Consequences
Daniel, R., & Smith, J. A. (2008) · Human Gene Therapy · doi:10.1089/hum.2007.148 · Cited by 73 · see citing works
Mattout, A., Goldberg, M., Tzur, Y. B., Margalit, A., & Gruenbaum, Y. (2006) · Journal of Cell Science · doi:10.1242/jcs.03325 · Cited by 73 · see citing works
The role of integration and clonal expansion in HIV infection: live long and prosper
Anderson, E. M., & Maldarelli, F. M. (2018) · Retrovirology · doi:10.1186/s12977-018-0448-8 · Cited by 72 · see citing works
Transcription Factors in Cancer: When Alternative Splicing Determines Opposite Cell Fates
Belluti, S., Rigillo, G., & Imbriano, C. (2020) · Cells · doi:10.3390/cells9030760 · Cited by 72 · see citing works
Al‐Mawsawi, L. Q., & Neamati, N. (2007) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2007.09.005 · Cited by 71 · see citing works
Fadel, H. J., Morrison, J. H., Saenz, D. T., Fuchs, J. R., Kvaratskhelia, M., Ekker, S. C., & Poeschla, E. M. (2014) · Journal of Virology · doi:10.1128/jvi.01397-14 · Cited by 69 · see citing works
LEDGF/p75 Proteins with Alternative Chromatin Tethers Are Functional HIV-1 Cofactors
Meehan, A. M., Saenz, D. T., Morrison, J. H., Garcia-Rivera, J. A., Peretz, M., Llano, M., & Poeschla, E. M. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000522 · Cited by 67 · see citing works
Hughes, S., Jenkins, V. A., Dar, M. J., Engelman, A., & Cherepanov, P. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.036491 · Cited by 65 · see citing works
Papayannakos, C. J., & Daniel, R. (2012) · Gene Therapy · doi:10.1038/gt.2012.88 · Cited by 66 · see citing works
Serrao, E., Krishnan, L., Shun, M.-C., Li, X., Cherepanov, P., Engelman, A., & Maertens, G. N. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku136 · Cited by 59 · see citing works
Rahman, S., Lu, R., Vandegraaff, N., Cherepanov, P., & Engelman, A. (2006) · Virology · doi:10.1016/j.virol.2006.08.011 · Cited by 64 · see citing works
Botbol, Y. M., Raghavendra, N. K., Rahman, S., Engelman, A., & Lavigne, M. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm1127 · Cited by 63 · see citing works
Ciuffi, A., Diamond, T. L., Hwang, Y. S., Marshall, H. M., & Bushman, F. D. (2006) · Human Gene Therapy · doi:10.1089/hum.2006.17.960 · Cited by 62 · see citing works
Hendrix, J., Gijsbers, R., Rijck, J. D., Voet, A. R. D., Hotta, J., McNeely, M., Hofkens, J., Debyser, Z., & Engelborghs, Y. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq933 · Cited by 57 · see citing works
Pandey, K. K., Sinha, S., & Grandgenett, D. P. (2007) · Journal of Virology · doi:10.1128/jvi.02322-06 · Cited by 58 · see citing works
Hibiya, K., Katsumoto, T., Kondo, T., Kitabayashi, I., & Kudō, A. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2009.02.021 · Cited by 56 · see citing works
The extended AT-hook is a novel RNA binding motif
Filarsky, M., Zillner, K., Araya, I., Villar‐Garea, A., Merkl, R., Längst, G., & Németh, A. (2015) · RNA Biology · doi:10.1080/15476286.2015.1060394 · Cited by 55 · see citing works
Reading More than Histones: The Prevalence of Nucleic Acid Binding among Reader Domains
Weaver, T., Morrison, E. A., & Musselman, C. A. (2018) · Molecules · doi:10.3390/molecules23102614 · Cited by 54 · see citing works
Leoh, L. S., van Heertum, B., Rijck, J. D., Filippova, M., Ríos-Colón, L., Basu, A., Martinez, S. R., Tungteakkhun, S. S., Filippov, V., Christ, F., et al. (2012) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-11-0314 · Cited by 52 · see citing works
Cohen, B., Addadi, Y., Sapoznik, S., Meir, G., Kalchenko, V., Harmelin, A., Ben‐Dor, S., & Neeman, M. (2009) · Neoplasia · doi:10.1593/neo.09636 · Cited by 51 · see citing works
Ortiz-Hernández, G. L., Sanchez-Hernández, E. S., & Casiano, C. A. (2020) · Autoimmunity Highlights · doi:10.1186/s13317-020-0126-4 · Cited by 50 · see citing works
Sapoznik, S., Cohen, B., Tzuman, Y. C., Meir, G., Ben‐Dor, S., Harmelin, A., & Neeman, M. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-1213 · Cited by 50 · see citing works
Lentiviral nuclear import: a complex interplay between virus and host
Rijck, J. D., Vandekerckhove, L., Christ, F., & Debyser, Z. (2007) · BioEssays · doi:10.1002/bies.20561 · Cited by 48 · see citing works
Bimodal high-affinity association of Brd4 with murine leukemia virus integrase and mononucleosomes
Larue, R. C., Plumb, M. R., Crowe, B. L., Shkriabai, N., Sharma, A., DiFiore, J., Malani, N., Aiyer, S. S., Roth, M. J., Bushman, F. D., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku135 · Cited by 44 · see citing works
Gijsbers, R., Vets, S., Rijck, J. D., Ocwieja, K. E., Ronen, K., Malani, N., Bushman, F. D., & Debyser, Z. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.255711 · Cited by 42 · see citing works
RetractedPrizan-Ravid, A., Elis, E., Laham-Karam, N., Selig, S., Ehrlich, M., & Bacharach, E. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1001183 · Cited by 43 · see citing works
Raghavendra, N. K., & Engelman, A. (2007) · Virology · doi:10.1016/j.virol.2006.12.022 · Cited by 43 · see citing works
Factors that mold the nuclear landscape of HIV-1 integration
Bedwell, G. J., & Engelman, A. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa1207 · Cited by 40 · see citing works
Brown‐Bryan, T. A., Leoh, L. S., Ganapathy, V., Pacheco, F. J., Mediavilla-Varela, M., Filippova, M., Linkhart, T. A., Gijsbers, R., Debyser, Z., & Casiano, C. A. (2008) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-08-0125 · Cited by 40 · see citing works
Nuclear protein LEDGF/p75 recognizes supercoiled DNA by a novel DNA-binding domain
Tsutsui, K., Sano, K., Hosoya, O., Miyamoto, T., & Tsutsui, K. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr088 · Cited by 40 · see citing works
GS-9822, a Preclinical LEDGIN Candidate, Displays a Block-and-Lock Phenotype in Cell Culture
Bruggemans, A., Vansant, G., Balakrishnan, M., Mitchell, M. L., Cai, R., Christ, F., & Debyser, Z. (2021) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02328-20 · Cited by 35 · see citing works
Meehan, A. M., Saenz, D. T., Morrison, J. H., Hu, C., Peretz, M., & Poeschla, E. M. (2011) · Journal of Virology · doi:10.1128/jvi.01295-10 · Cited by 33 · see citing works
Inhibitors of the Interactions between HIV‐1 IN and the Cofactor LEDGF/p75
Luca, L. D., Ferro, S., Morreale, F. E., Grazia, S. D., & Chimirri, A. (2011) · ChemMedChem · doi:10.1002/cmdc.201100071 · Cited by 36 · see citing works
DNA Binding Properties of TAF1 Isoforms with Two AT-hooks
Metcalf, C. E., & Wassarman, D. A. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m606289200 · Cited by 34 · see citing works
Strategies for Targeting Retroviral Integration for Safer Gene Therapy: Advances and Challenges
Yoder, K. E., Rabe, A. J., Fishel, R. A., & Larue, R. C. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.662331 · Cited by 34 · see citing works
Bueno, M. T. D., Garcia-Rivera, J. A., Kugelman, J. R., Morales, E., Rosas-Acosta, G., & Llano, M. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.03.063 · Cited by 33 · see citing works
In search of small molecules blocking interactions between HIV proteins and intracellularcofactors
Busschots, K., Rijck, J. D., Christ, F., & Debyser, Z. (2008) · Molecular BioSystems · doi:10.1039/b810306b · Cited by 34 · see citing works
Virological and Cellular Roles of the Transcriptional Coactivator LEDGF/p75
Llano, M., Morrison, J. H., & Poeschla, E. M. (2009) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-02175-6_7 · Cited by 33 · see citing works
Dynamic Oligomerization of Integrase Orchestrates HIV Nuclear Entry
Borrenberghs, D., Dirix, L., Wit, F. D., Rocha, S., Blokken, J., Houwer, S. D., Gijsbers, R., Christ, F., Hofkens, J., Hendrix, J., et al. (2016) · Scientific Reports · doi:10.1038/srep36485 · Cited by 31 · see citing works
In Vitro DNA Tethering of HIV-1 Integrase by the Transcriptional Coactivator LEDGF/p75
McNeely, M., Hendrix, J., Busschots, K., Boons, E., Deleersnijder, A., Gérard, M., Christ, F., & Debyser, Z. (2011) · Journal of Molecular Biology · doi:10.1016/j.jmb.2011.03.073 · Cited by 32 · see citing works
Malyavantham, K. S., & Suresh, L. (2017) · Autoimmunity Highlights · doi:10.1007/s13317-017-0091-8 · Cited by 32 · see citing works
Janssens, J., De Wit, F., Parveen, N., & Debyser, Z. (2022) · mBio · doi:10.1128/mbio.00007-22 · Cited by 28 · see citing works
Cryo-EM structure of the deltaretroviral intasome in complex with the PP2A regulatory subunit B56γ
Barski, M. S., Minnell, J. J., Hodakova, Z., Pye, V. E., Nans, A., Cherepanov, P., & Maertens, G. N. (2020) · Nature Communications · doi:10.1038/s41467-020-18874-y · Cited by 29 · see citing works
Vanderlinden, W., Lipfert, J., Demeulemeester, J., Debyser, Z., & Feyter, S. D. (2014) · Nanoscale · doi:10.1039/c4nr00022f · Cited by 31 · see citing works
Protein–protein and protein–chromatin interactions of LEDGF/p75 as novel drug targets
Blokken, J., Rijck, J. D., Christ, F., & Debyser, Z. (2017) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2017.11.002 · Cited by 31 · see citing works
Integration of HIV-1 DNA Is Regulated by Interplay between Viral Rev and Cellular LEDGF/p75 Proteins
Levin, A., Rosenbluh, J., Hayouka, Z., Friedler, A., & Loyter, A. (2009) · Molecular Medicine · doi:10.2119/molmed.2009.00133 · Cited by 30 · see citing works
Feline Central Retinal Degeneration
Bellhorn, R. W., & Fischer, C. A. (1970) · Journal of the American Veterinary Medical Association · doi:10.2460/javma.1970.157.06.842 · Cited by 30 · see citing works
Darvekar, S. R., Sagen-Johnsen, S., Eriksen, A. B., Johansen, T., & Sjøttem, E. (2011) · Biochemical Journal · doi:10.1042/bj20111230 · Cited by 29 · see citing works
Naughtin, M., Haftek-Terreau, Z., Xavier, J., Meyer, S., Silvain, M., Jaszczyszyn, Y., Levy, N., Miele, V., Benleulmi, M. S., Ruff, M., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0129427 · Cited by 28 · see citing works
Sites of retroviral DNA integration: From basic research to clinical applications
Serrao, E., & Engelman, A. (2015) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2015.1102859 · Cited by 28 · see citing works
- Authors
- Turlure, F.
- Affiliations
- Dana-Farber Cancer Institute (US)
- Corresponding author
- Turlure, F.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-03-06
- Volume
- 34
- Issue
- 5
- Pages
- 1653-1665
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC1405818
- OpenAlex
- W2059740818
- Cited by
- 181
- References
- 55
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 7 · 2023: 4 · 2022: 7 · 2021: 5 · 2020: 8 · 2019: 3 · 2018: 8 · 2017: 4 · 2016: 5 · 2015: 10 · 2014: 15 · 2013: 7 · 2012: 13
- FWCI
- 6.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- other-oa
- Locations
- Nucleic Acids Research (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Funders
- National Institutes of Health
- Center for AIDS Research, University of Washington
- National Institute of Allergy and Infectious Diseases (AI52014, AI60354, AI39394, R01AI039394, R37AI039394, R01AI052014, P30AI060354)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- LEDGF/p75, nuclear localization signal, AT-hook motif, nonspecific DNA binding, chromatin association, PWWP domain, HIV-1 integrase, transcriptional coactivator, metaphase chromosomes
- MeSH terms
- Amino Acid Sequence, Binding Sites, Chromatin, DNA, DNA-Binding Proteins, HeLa Cells, Humans, Molecular Sequence Data, Transcription Factors, Consensus Sequence, Protein Structure, Tertiary, HIV Integrase, Nuclear Localization Signals, AT-Hook Motifs, Adaptor Proteins, Signal Transducing
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