PSIP1

Summary

Gene Symbol: PSIP1
Description: PC4 and SFRS1 interacting protein 1
Alias: DFS70, LEDGF, PAIP, PSIP2, p52, p75, PC4 and SFRS1-interacting protein, CLL-associated antigen KW-7, dense fine speckles 70 kDa protein, lens epithelium-derived growth factor, transcriptional coactivator p52/p75
Species: human
Products:     PSIP1

Top Publications

  1. Schrijvers R, Demeulemeester J, De Rijck J, Christ F, Gerard M, Debyser Z, et al. Characterization of rare lens epithelium-derived growth factor/p75 genetic variants identified in HIV-1 long-term nonprogressors. AIDS. 2013;27:539-43 pubmed publisher
    Lens epithelium-derived growth factor (LEDGF)/p75 is a cellular binding partner of HIV-1 integrase and a crucial cofactor for HIV-1 replication...
  2. Garcia Rivera J, Bueno M, Morales E, Kugelman J, Rodriguez D, Llano M. Implication of serine residues 271, 273, and 275 in the human immunodeficiency virus type 1 cofactor activity of lens epithelium-derived growth factor/p75. J Virol. 2010;84:740-52 pubmed publisher
    Lens epithelium-derived growth factor (LEDGF)/p75 is a cellular cofactor for HIV-1 DNA integration...
  3. Tsiang M, Jones G, Niedziela Majka A, Kan E, Lansdon E, Huang W, et al. New class of HIV-1 integrase (IN) inhibitors with a dual mode of action. J Biol Chem. 2012;287:21189-203 pubmed publisher
    ..LEDGINs are a class of potent antiviral compounds that interacts with the lens epithelium-derived growth factor (LEDGF) binding pocket on IN and were identified through competition binding against LEDGF...
  4. Llano M, Vanegas M, Hutchins N, Thompson D, Delgado S, Poeschla E. Identification and characterization of the chromatin-binding domains of the HIV-1 integrase interactor LEDGF/p75. J Mol Biol. 2006;360:760-73 pubmed
    Depletion of the transcriptional co-activator LEDGF/p75 by RNA interference alters the genome-wide pattern of HIV-1 integration, reducing integration into active genes, reducing integration into LEDGF/p75-regulated genes, and increasing ..
  5. Nishizawa Y, Usukura J, Singh D, Chylack L, Shinohara T. Spatial and temporal dynamics of two alternatively spliced regulatory factors, lens epithelium-derived growth factor (ledgf/p75) and p52, in the nucleus. Cell Tissue Res. 2001;305:107-14 pubmed
    Regulatory factors, lens epithelium-derived growth factor (LEDGF)/p75 and p52, are generated from a single LEDGF gene by alternative splicing...
  6. Du L, Zhao Y, Chen J, Yang L, Zheng Y, Tang Y, et al. D77, one benzoic acid derivative, functions as a novel anti-HIV-1 inhibitor targeting the interaction between integrase and cellular LEDGF/p75. Biochem Biophys Res Commun. 2008;375:139-44 pubmed publisher
    ..In this process, Lens epithelium-derived growth factor (LEDGF/p75) is discovered to function as a cellular co-factor for integration...
  7. Kessl J, Li M, Ignatov M, Shkriabai N, Eidahl J, Feng L, et al. FRET analysis reveals distinct conformations of IN tetramers in the presence of viral DNA or LEDGF/p75. Nucleic Acids Res. 2011;39:9009-22 pubmed publisher
    ..b>LEDGF/p75, a key cellular binding partner of the lentiviral enzyme, also stabilizes a tetrameric form of IN...
  8. Ochs R, Muro Y, Si Y, Ge H, Chan E, Tan E. Autoantibodies to DFS 70 kd/transcription coactivator p75 in atopic dermatitis and other conditions. J Allergy Clin Immunol. 2000;105:1211-20 pubmed
    ..A serum containing high-titer antibodies to DFS70 was used to immunoscreen a complementary (c)DNA expression library to isolate cDNA encoding the antigen...
  9. Huang T, Myklebust L, Kjarland E, Gjertsen B, Pendino F, Bruserud Ø, et al. LEDGF/p75 has increased expression in blasts from chemotherapy-resistant human acute myelogenic leukemia patients and protects leukemia cells from apoptosis in vitro. Mol Cancer. 2007;6:31 pubmed
    ..transcription factors ERF-2/TIS11d, and the p75 and p52 splice variants of Lens Epithelial Derived Growth Factor (LEDGF)...

More Information

Publications115 found, 100 shown here

  1. McKee C, Kessl J, Shkriabai N, Dar M, Engelman A, Kvaratskhelia M. Dynamic modulation of HIV-1 integrase structure and function by cellular lens epithelium-derived growth factor (LEDGF) protein. J Biol Chem. 2008;283:31802-12 pubmed publisher
    ..Among these, LEDGF has been identified as a cellular cofactor critical for effective HIV-1 integration...
  2. Desimmie B, Schrijvers R, Demeulemeester J, Borrenberghs D, Weydert C, Thys W, et al. LEDGINs inhibit late stage HIV-1 replication by modulating integrase multimerization in the virions. Retrovirology. 2013;10:57 pubmed publisher
    LEDGINs are novel allosteric HIV integrase (IN) inhibitors that target the lens epithelium-derived growth factor (LEDGF)/p75 binding pocket of IN...
  3. Shun M, Botbol Y, Li X, Di Nunzio F, Daigle J, Yan N, et al. Identification and characterization of PWWP domain residues critical for LEDGF/p75 chromatin binding and human immunodeficiency virus type 1 infectivity. J Virol. 2008;82:11555-67 pubmed publisher
    Lens epithelium-derived growth factor (LEDGF)/p75 functions as a bimodal tether during lentiviral DNA integration: its C-terminal integrase-binding domain interacts with the viral preintegration complex, whereas the N-terminal PWWP ..
  4. Allouch A, Cereseto A. Identification of cellular factors binding to acetylated HIV-1 integrase. Amino Acids. 2011;41:1137-45 pubmed publisher
    ..Nevertheless, few two-hybrid hits bind with the same affinity the acetylated and the unmodified IN. These results further underlie the relevance of IN post-translational modification by acetylation in HIV-1 replication cycle. ..
  5. Bhargavan B, Fatma N, Chhunchha B, Singh V, Kubo E, Singh D. LEDGF gene silencing impairs the tumorigenicity of prostate cancer DU145 cells by abating the expression of Hsp27 and activation of the Akt/ERK signaling pathway. Cell Death Dis. 2012;3:e316 pubmed publisher
    Lens epithelium-derived growth factor (LEDGF) maintains survival pathways by augmenting the transcription of stress-response genes such as small heat-shock protein 27...
  6. Hendrix J, Gijsbers R, De Rijck J, Voet A, Hotta J, McNeely M, et al. The transcriptional co-activator LEDGF/p75 displays a dynamic scan-and-lock mechanism for chromatin tethering. Nucleic Acids Res. 2011;39:1310-25 pubmed publisher
    ..cellular and disease related functions of the transcriptional co-activator lens epithelium-derived growth factor (LEDGF/p75) involve tethering of interaction partners to chromatin via its conserved integrase binding domain (IBD), but ..
  7. Hou Y, McGuinness D, Prongay A, Feld B, Ingravallo P, Ogert R, et al. Screening for antiviral inhibitors of the HIV integrase-LEDGF/p75 interaction using the AlphaScreen luminescent proximity assay. J Biomol Screen. 2008;13:406-14 pubmed publisher
    ..for identification of HIV integrase inhibitors, targeting the interaction between HIV IN and the cellular cofactor LEDGF/p75...
  8. Wu X, Daniels T, Molinaro C, Lilly M, Casiano C. Caspase cleavage of the nuclear autoantigen LEDGF/p75 abrogates its pro-survival function: implications for autoimmunity in atopic disorders. Cell Death Differ. 2002;9:915-25 pubmed
    Lens epithelium-derived growth factor p75 (LEDGF/p75) is a nuclear autoantigen in atopic disorders implicated in cellular protection against stress-induced apoptosis...
  9. Karki R, Tang Y, Burke T, Nicklaus M. Model of full-length HIV-1 integrase complexed with viral DNA as template for anti-HIV drug design. J Comput Aided Mol Des. 2004;18:739-60 pubmed
    ..The results indicate that the diketo-acid IN inhibitors probably chelate the metal ion in the catalytic site and also prevent the exposure of the 3'-processed end of the viral DNA to human DNA. ..
  10. Vandegraaff N, Devroe E, Turlure F, Silver P, Engelman A. Biochemical and genetic analyses of integrase-interacting proteins lens epithelium-derived growth factor (LEDGF)/p75 and hepatoma-derived growth factor related protein 2 (HRP2) in preintegration complex function and HIV-1 replication. Virology. 2006;346:415-26 pubmed
    ..Lens epithelium-derived growth factor (LEDGF) transcriptional coactivator/p75 and hepatoma-derived growth factor related protein 2 (HRP2) tightly bind to HIV-1 ..
  11. Suzuki Y, Craigie R. The road to chromatin - nuclear entry of retroviruses. Nat Rev Microbiol. 2007;5:187-96 pubmed
    ..Before integration into the host genome can occur, this complex must be transported to the nucleus and must cross the nuclear envelope. This Review summarizes our current knowledge of how this journey is accomplished. ..
  12. De Luca L, Barreca M, Ferro S, Christ F, Iraci N, Gitto R, et al. Pharmacophore-based discovery of small-molecule inhibitors of protein-protein interactions between HIV-1 integrase and cellular cofactor LEDGF/p75. ChemMedChem. 2009;4:1311-6 pubmed publisher
    The cellular protein lens epithelium-derived growth factor, or transcriptional coactivator p75 (LEDGF/p75), plays a crucial role in HIV integration...
  13. Mous K, Jennes W, Camara M, Seydi M, Daneau G, Mboup S, et al. Expression analysis of LEDGF/p75, APOBEC3G, TRIM5alpha, and tetherin in a Senegalese cohort of HIV-1-exposed seronegative individuals. PLoS ONE. 2012;7:e33934 pubmed publisher
    ..Lens epithelium-derived growth factor (LEDGF/p75) benefits HIV, whereas apolipoprotein B mRNA-editing catalytic polypeptide-like 3G (APOBEC3G), tripartite ..
  14. Meehan A, Saenz D, Morrison J, Garcia Rivera J, Peretz M, Llano M, et al. LEDGF/p75 proteins with alternative chromatin tethers are functional HIV-1 cofactors. PLoS Pathog. 2009;5:e1000522 pubmed publisher
    b>LEDGF/p75 can tether over-expressed lentiviral integrase proteins to chromatin but how this underlies its integration cofactor role for these retroviruses is unclear...
  15. Brown Bryan T, Leoh L, Ganapathy V, Pacheco F, Mediavilla Varela M, Filippova M, et al. Alternative splicing and caspase-mediated cleavage generate antagonistic variants of the stress oncoprotein LEDGF/p75. Mol Cancer Res. 2008;6:1293-307 pubmed publisher
    ..Lens epithelium-derived growth factor p75 (LEDGF/p75), also known as DFS70 autoantigen, is emerging as a survival oncoprotein that promotes resistance to oxidative stress-induced cell death ..
  16. Levin A, Rosenbluh J, Hayouka Z, Friedler A, Loyter A. Integration of HIV-1 DNA is regulated by interplay between viral rev and cellular LEDGF/p75 proteins. Mol Med. 2010;16:34-44 pubmed publisher
    ..immunodeficiency virus type 1 (HIV-1) Rev protein and the cellular lens epithelium-derived growth factor p75 (LEDGF/p75) protein in vitro and in virus-infected cells...
  17. Lewinski M, Bushman F. Retroviral DNA integration--mechanism and consequences. Adv Genet. 2005;55:147-81 pubmed
    ..Research into the mechanisms of retroviral integration site selection has shed light on the phenomena of insertional mutagenesis and viral latency. ..
  18. Ciuffi A, Llano M, Poeschla E, Hoffmann C, Leipzig J, Shinn P, et al. A role for LEDGF/p75 in targeting HIV DNA integration. Nat Med. 2005;11:1287-9 pubmed
    ..Cellular lens epithelium-derived growth factor (LEDGF/p75) binds both chromosomal DNA and HIV integrase, and might therefore direct integration by a tethering ..
  19. Cherepanov P, Devroe E, Silver P, Engelman A. Identification of an evolutionarily conserved domain in human lens epithelium-derived growth factor/transcriptional co-activator p75 (LEDGF/p75) that binds HIV-1 integrase. J Biol Chem. 2004;279:48883-92 pubmed
    Human lens epithelium-derived growth factor/transcriptional co-activator p75 (LEDGF/p75) protein was recently identified as a binding partner for HIV-1 integrase (IN) in human cells...
  20. Gupta K, Diamond T, Hwang Y, Bushman F, Van Duyne G. Structural properties of HIV integrase. Lens epithelium-derived growth factor oligomers. J Biol Chem. 2010;285:20303-15 pubmed publisher
    ..of human immunodeficiency virus IN alone and its complex with the integrase binding domain of the host factor PSIP1/lens epithelium-derived growth factor (LEDGF)/p75 are available, many questions remain regarding the properties ..
  21. Christ F, Shaw S, Demeulemeester J, Desimmie B, Marchand A, Butler S, et al. Small-molecule inhibitors of the LEDGF/p75 binding site of integrase block HIV replication and modulate integrase multimerization. Antimicrob Agents Chemother. 2012;56:4365-74 pubmed publisher
    ..acid derivatives, blocking HIV replication at a low micromolar concentration through binding in the LEDGF/p75 binding pocket of HIV integrase, hence referred to as LEDGINs...
  22. McNeely M, Hendrix J, Busschots K, Boons E, Deleersnijder A, Gerard M, et al. In vitro DNA tethering of HIV-1 integrase by the transcriptional coactivator LEDGF/p75. J Mol Biol. 2011;410:811-30 pubmed publisher
    Although LEDGF/p75 is believed to act as a cellular cofactor of lentiviral integration by tethering integrase (IN) to chromatin, there is no good in vitro model to analyze this functionality...
  23. Gérard A, Soler N, Segeral E, Belshan M, Emiliani S. Identification of low molecular weight nuclear complexes containing integrase during the early stages of HIV-1 infection. Retrovirology. 2013;10:13 pubmed publisher
    ..Interactions between IN and cellular cofactors LEDGF/p75 and TNPO3 were detected as early as 6?h post-infection...
  24. Das S, Kalpana G. Reverse two-hybrid screening to analyze protein-protein interaction of HIV-1 viral and cellular proteins. Methods Mol Biol. 2009;485:271-93 pubmed publisher
    ..Once the mutants are isolated, they are tested in other biochemical systems and can be subjected to further functional and virological studies. ..
  25. Madlala P, Gijsbers R, Christ F, Hombrouck A, Werner L, Mlisana K, et al. Association of polymorphisms in the LEDGF/p75 gene (PSIP1) with susceptibility to HIV-1 infection and disease progression. AIDS. 2011;25:1711-9 pubmed publisher
    b>LEDGF/p75, encoded by the PSIP1 gene, interacts with HIV-1 integrase and targets HIV-1 integration into active genes...
  26. Bueno M, Garcia Rivera J, Kugelman J, Morales E, Rosas Acosta G, Llano M. SUMOylation of the lens epithelium-derived growth factor/p75 attenuates its transcriptional activity on the heat shock protein 27 promoter. J Mol Biol. 2010;399:221-39 pubmed publisher
    Lens epithelium-derived growth factor (LEDGF) proteins p75 and p52 are transcriptional coactivators that connect sequence-specific activators to the basal transcription machinery...
  27. Takeichi T, Sugiura K, Muro Y, Matsumoto K, Ogawa Y, Futamura K, et al. Overexpression of LEDGF/DFS70 induces IL-6 via p38 activation in HaCaT cells, similar to that seen in the psoriatic condition. J Invest Dermatol. 2010;130:2760-7 pubmed publisher
    Lens epithelium-derived growth factor (LEDGF)/dense fine speckles 70? kDa protein (DFS70) is a transcription cofactor that enhances growth and is overexpressed in various cancers...
  28. Christ F, Debyser Z. The LEDGF/p75 integrase interaction, a novel target for anti-HIV therapy. Virology. 2013;435:102-9 pubmed publisher
    ..Lens Epithelium-derived Growth factor (LEDGF/p75), a transcriptional co-activator, is a co-factor of HIV-integrase (IN) and is required for the tethering and ..
  29. Vandekerckhove L, Christ F, Van Maele B, De Rijck J, Gijsbers R, Van den Haute C, et al. Transient and stable knockdown of the integrase cofactor LEDGF/p75 reveals its role in the replication cycle of human immunodeficiency virus. J Virol. 2006;80:1886-96 pubmed
    After identifying the interaction between the transcriptional coactivator lens epithelium-derived growth factor (LEDGF/p75) and the human immunodeficiency virus type 1 (HIV-1) integrase (IN), we have now investigated the role of LEDGF/..
  30. Yu F, Jones G, Hung M, Wagner A, Macarthur H, Liu X, et al. HIV-1 integrase preassembled on donor DNA is refractory to activity stimulation by LEDGF/p75. Biochemistry. 2007;46:2899-908 pubmed
    b>LEDGF/p75 is known to enhance the integrase strand transfer activity in vitro, but the underlying mechanism is unclear...
  31. Tsiang M, Jones G, Hung M, Mukund S, Han B, Liu X, et al. Affinities between the binding partners of the HIV-1 integrase dimer-lens epithelium-derived growth factor (IN dimer-LEDGF) complex. J Biol Chem. 2009;284:33580-99 pubmed publisher
    The interaction between lens epithelium-derived growth factor/transcriptional co-activator p75 (LEDGF) and human immunodeficiency virus type 1 (HIV-1) integrase (IN) is essential for HIV-1 replication...
  32. Hare S, Cherepanov P. The Interaction Between Lentiviral Integrase and LEDGF: Structural and Functional Insights. Viruses. 2009;1:780-801 pubmed publisher
    Since its initial description as an HIV-1 integrase (IN) interactor seven years ago, LEDGF has become one of the best-characterized host factors involved in viral replication...
  33. Botbol Y, Raghavendra N, Rahman S, Engelman A, Lavigne M. Chromatinized templates reveal the requirement for the LEDGF/p75 PWWP domain during HIV-1 integration in vitro. Nucleic Acids Res. 2008;36:1237-46 pubmed publisher
    ..in the retroviral lifecycle, and the lentiviral integrase binding protein lens epithelium-derived growth factor (LEDGF)/p75 plays a crucial role during human immunodeficiency virus type 1 (HIV-1) cDNA integration...
  34. Fan X, Zhang F, Al Safi R, Zeng L, Shabaik Y, Debnath B, et al. Design of HIV-1 integrase inhibitors targeting the catalytic domain as well as its interaction with LEDGF/p75: a scaffold hopping approach using salicylate and catechol groups. Bioorg Med Chem. 2011;19:4935-52 pubmed publisher
    ..the design and discovery of novel IN inhibitors targeting the catalytic domain as well as its interaction with LEDGF/p75, which is essential for the HIV-1 integration as an IN cofactor...
  35. Xu Z, Zheng Y, Ao Z, Clement M, Mouland A, Kalpana G, et al. Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. Retrovirology. 2008;5:102 pubmed publisher
    ..Additionally, we determined that while these IN mutants failed to interact with LEDGF/p75, they retained the ability to bind Integrase interactor 1...
  36. De Luca L, Ferro S, Morreale F, De Grazia S, Chimirri A. Inhibitors of the interactions between HIV-1 IN and the cofactor LEDGF/p75. ChemMedChem. 2011;6:1184-91 pubmed publisher
    ..The nuclear protein lens epithelium-derived growth factor (LEDGF/p75) is a multidomain protein, present in host cells, which plays an important role in the integration process...
  37. Leoh L, van Heertum B, De Rijck J, Filippova M, Ríos Colón L, Basu A, et al. The stress oncoprotein LEDGF/p75 interacts with the methyl CpG binding protein MeCP2 and influences its transcriptional activity. Mol Cancer Res. 2012;10:378-91 pubmed publisher
    The lens epithelium-derived growth factor p75 (LEDGF/p75) is a transcription coactivator that promotes resistance to oxidative stress- and chemotherapy-induced cell death...
  38. Hu G, Li X, Sun X, Lu W, Liu G, Huang J, et al. Identification of old drugs as potential inhibitors of HIV-1 integrase - human LEDGF/p75 interaction via molecular docking. J Mol Model. 2012;18:4995-5003 pubmed publisher
    ..In this process, human protein Lens epithelium-derived growth factor (LEDGF/p75) is discovered to function as a cellular co-factor for integration...
  39. Cherepanov P, Maertens G, Proost P, Devreese B, Van Beeumen J, Engelborghs Y, et al. HIV-1 integrase forms stable tetramers and associates with LEDGF/p75 protein in human cells. J Biol Chem. 2003;278:372-81 pubmed
    ..This novel integrase interacting protein was found to be identical to lens epithelium-derived growth factor (LEDGF/p75), a protein implicated in regulation of gene expression and cellular stress response...
  40. Ge H, Si Y, Roeder R. Isolation of cDNAs encoding novel transcription coactivators p52 and p75 reveals an alternate regulatory mechanism of transcriptional activation. EMBO J. 1998;17:6723-9 pubmed
    ..Here, we report the isolation of cDNAs encoding two novel human transcriptional coactivators (p52 and p75) that are derived from alternatively spliced products of a single gene and share a region of 325 residues, ..
  41. Takamura Y, Fatma N, Kubo E, Singh D. Regulation of heavy subunit chain of gamma-glutamylcysteine synthetase by tumor necrosis factor-alpha in lens epithelial cells: role of LEDGF/p75. Am J Physiol Cell Physiol. 2006;290:C554-66 pubmed
    ..Lens epithelium-derived growth factor (LEDGF)/p75, a transcriptional protein, is inducible by oxidative stress and protects cells from various stresses by ..
  42. Poeschla E. Integrase, LEDGF/p75 and HIV replication. Cell Mol Life Sci. 2008;65:1403-24 pubmed publisher
    ..Among implicated cellular factors, much recent attention has coalesced around LEDGF/p75, a nuclear protein that may act as a chromatin docking factor or receptor for lentiviral pre-integration ..
  43. Hughes S, Jenkins V, Dar M, Engelman A, Cherepanov P. Transcriptional co-activator LEDGF interacts with Cdc7-activator of S-phase kinase (ASK) and stimulates its enzymatic activity. J Biol Chem. 2010;285:541-54 pubmed publisher
    Lens epithelium-derived growth factor (LEDGF) is an important co-factor of human immunodeficiency virus DNA integration; however, its cellular functions are poorly characterized...
  44. Morerio C, Acquila M, Rosanda C, Rapella A, Tassano E, Micalizzi C, et al. t(9;11)(p22;p15) with NUP98-LEDGF fusion gene in pediatric acute myeloid leukemia. Leuk Res. 2005;29:467-70 pubmed
    ..We report a novel fusion of the NUP98 and LEDGF genes in a pediatric AML with intermediate characteristics between M2-M3 French-American-British (FAB) subtypes ..
  45. Sapoznik S, Cohen B, Tzuman Y, Meir G, Ben Dor S, Harmelin A, et al. Gonadotropin-regulated lymphangiogenesis in ovarian cancer is mediated by LEDGF-induced expression of VEGF-C. Cancer Res. 2009;69:9306-14 pubmed publisher
    ..Seeking the molecular mechanism, we examined the role of lens epithelium-derived growth factor (LEDGF/p75) and the possible contribution of its putative target, a conserved stress-response element identified in ..
  46. Singh D, Kimura A, Chylack L, Shinohara T. Lens epithelium-derived growth factor (LEDGF/p75) and p52 are derived from a single gene by alternative splicing. Gene. 2000;242:265-73 pubmed
    A human gene that encodes lens epithelium-derived growth factor (LEDGF) was isolated, and the DNA sequence and the exon/intron organization was determined...
  47. Bartholomeeusen K, De Rijck J, Busschots K, Desender L, Gijsbers R, Emiliani S, et al. Differential interaction of HIV-1 integrase and JPO2 with the C terminus of LEDGF/p75. J Mol Biol. 2007;372:407-21 pubmed
    The transcriptional co-activator lens epithelium-derived growth factor (LEDGF) has been shown to protect cells against environmental stress...
  48. Kessl J, Jena N, Koh Y, Taskent Sezgin H, Slaughter A, Feng L, et al. Multimode, cooperative mechanism of action of allosteric HIV-1 integrase inhibitors. J Biol Chem. 2012;287:16801-11 pubmed publisher
    The multifunctional HIV-1 enzyme integrase interacts with viral DNA and its key cellular cofactor LEDGF to effectively integrate the reverse transcript into a host cell chromosome...
  49. Busschots K, Voet A, De Maeyer M, Rain J, Emiliani S, Benarous R, et al. Identification of the LEDGF/p75 binding site in HIV-1 integrase. J Mol Biol. 2007;365:1480-92 pubmed
    Lens epithelium-derived growth factor (LEDGF)/p75 is an important cellular co-factor for human immunodeficiency virus (HIV) replication. We originally identified LEDGF/p75 as a binding partner of integrase (IN) in human cells...
  50. Merad H, Porumb H, Zargarian L, René B, Hobaika Z, Maroun R, et al. An unusual helix turn helix motif in the catalytic core of HIV-1 integrase binds viral DNA and LEDGF. PLoS ONE. 2009;4:e4081 pubmed publisher
    ..range; 2- the whole IN enzyme; and 3- the IN binding domain (IBD) but not the IBD-Asp366Asn variant of LEDGF (lens epidermal derived growth factor) lacking the essential Asp366 residue...
  51. Zheng Y, Ao Z, Jayappa K, Yao X. Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. Virol J. 2010;7:68 pubmed publisher
    ..Previous studies have demonstrated that HIV-1 IN interacts with a cellular Lens epithelium-derived growth factor (LEDGF/p75) and that this viral/cellular interaction plays an important role for tethering HIV-1 preintegration complexes ..
  52. Singh D, Bhargavan B, Chhunchha B, Kubo E, Kumar A, Fatma N. Transcriptional protein Sp1 regulates LEDGF transcription by directly interacting with its cis-elements in GC-rich region of TATA-less gene promoter. PLoS ONE. 2012;7:e37012 pubmed publisher
    b>LEDGF/p75 interacts with DNA/protein to regulate gene expression and function. Despite the recognized diversity of function of LEDGF/p75, knowledge of its transregulation is in its infancy...
  53. Di Nunzio F. New insights in the role of nucleoporins: a bridge leading to concerted steps from HIV-1 nuclear entry until integration. Virus Res. 2013;178:187-96 pubmed publisher
    ..In particular, it will be reviewed both what is known and what is speculated about the link between HIV translocation through the nuclear pore and the proviral integration in the host chromatin. ..
  54. Singh D, Ohguro N, Kikuchi T, Sueno T, Reddy V, Yuge K, et al. Lens epithelium-derived growth factor: effects on growth and survival of lens epithelial cells, keratinocytes, and fibroblasts. Biochem Biophys Res Commun. 2000;267:373-81 pubmed
    ..library with antibody (Ab) from a cataract patient and named it "lens epithelium-derived growth factor" (LEDGF). LEDGF is found to be identical to p75, a coactivator of both transcription (1) and pre-mRNA splicing (2)...
  55. Llano M, Vanegas M, Fregoso O, Saenz D, Chung S, Peretz M, et al. LEDGF/p75 determines cellular trafficking of diverse lentiviral but not murine oncoretroviral integrase proteins and is a component of functional lentiviral preintegration complexes. J Virol. 2004;78:9524-37 pubmed
    ..The intracellular trafficking of each was determined instead by the transcriptional coactivator LEDGF/p75, which was required for nuclear localization...
  56. Busschots K, Vercammen J, Emiliani S, Benarous R, Engelborghs Y, Christ F, et al. The interaction of LEDGF/p75 with integrase is lentivirus-specific and promotes DNA binding. J Biol Chem. 2005;280:17841-7 pubmed
    ..previously shown that the p75 isoform of the transcriptional co-activator lens epithelium-derived growth factor (LEDGF) interacts tightly with human immunodeficiency virus (HIV)-1 integrase (IN) and is essential for nuclear targeting ..
  57. Maertens G, Cherepanov P, Debyser Z, Engelborghs Y, Engelman A. Identification and characterization of a functional nuclear localization signal in the HIV-1 integrase interactor LEDGF/p75. J Biol Chem. 2004;279:33421-9 pubmed
    Human lens epithelium-derived growth factor (LEDGF)/p75 protein forms a specific nuclear complex with human immunodeficiency virus type 1 (HIV-1) integrase and is essential for nuclear localization and chromosomal association of the ..
  58. Marshall H, Ronen K, Berry C, Llano M, Sutherland H, Saenz D, et al. Role of PSIP1/LEDGF/p75 in lentiviral infectivity and integration targeting. PLoS ONE. 2007;2:e1340 pubmed
    ..A cellular protein, PSIP1/LEDGF/p75, binds tightly to the lentiviral-encoded integrase protein (IN), and has been reported to be important for HIV ..
  59. Basu A, Rojas H, Banerjee H, Cabrera I, Perez K, De Leon M, et al. Expression of the stress response oncoprotein LEDGF/p75 in human cancer: a study of 21 tumor types. PLoS ONE. 2012;7:e30132 pubmed publisher
    ..The lens epithelium derived growth factor p75 (LEDGF/p75) is a transcription co-activator that promotes resistance to stress-induced cell ..
  60. De Rijck J, Vandekerckhove L, Gijsbers R, Hombrouck A, Hendrix J, Vercammen J, et al. Overexpression of the lens epithelium-derived growth factor/p75 integrase binding domain inhibits human immunodeficiency virus replication. J Virol. 2006;80:11498-509 pubmed
    We initially identified lens epithelium-derived growth factor/p75 (LEDGF/p75) as a binding partner of human immunodeficiency virus type 1 (HIV-1) integrase...
  61. Engelman A, Cherepanov P. The lentiviral integrase binding protein LEDGF/p75 and HIV-1 replication. PLoS Pathog. 2008;4:e1000046 pubmed publisher
    ..results have highlighted an important role for the integrase-interactor lens epithelium-derived growth factor (LEDGF)/p75 in lentiviral integration...
  62. Busschots K, De Rijck J, Christ F, Debyser Z. In search of small molecules blocking interactions between HIV proteins and intracellular cofactors. Mol Biosyst. 2009;5:21-31 pubmed publisher
    ..Our hypothesis will exemplify and discuss the interaction between HIV-1 integrase and its cellular cofactor LEDGF/p75, which, as evidenced by crystallography and site directed mutagenesis, displays favourable properties needed ..
  63. Li X, Koh Y, Engelman A. Correlation of recombinant integrase activity and functional preintegration complex formation during acute infection by replication-defective integrase mutant human immunodeficiency virus. J Virol. 2012;86:3861-79 pubmed publisher
    ..K264E integrase furthermore efficiently interacted in vitro with two heterologous binding partners, LEDGF/p75 and reverse transcriptase...
  64. Cherepanov P, Sun Z, Rahman S, Maertens G, Wagner G, Engelman A. Solution structure of the HIV-1 integrase-binding domain in LEDGF/p75. Nat Struct Mol Biol. 2005;12:526-32 pubmed
    Lens epithelium-derived growth factor (LEDGF)/p75 is the dominant binding partner of HIV-1 integrase (IN) in human cells...
  65. Hombrouck A, De Rijck J, Hendrix J, Vandekerckhove L, Voet A, De Maeyer M, et al. Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. PLoS Pathog. 2007;3:e47 pubmed
    ..Lentiviral integrases use the cellular protein LEDGF/p75 to tether the preintegration complex to the chromosome, although the existence of alternative host proteins ..
  66. Yokoyama A, Cleary M. Menin critically links MLL proteins with LEDGF on cancer-associated target genes. Cancer Cell. 2008;14:36-46 pubmed publisher
    ..serve as a molecular adaptor that physically links the MLL (mixed-lineage leukemia) histone methyltransferase with LEDGF (lens epithelium-derived growth factor), a chromatin-associated protein previously implicated in leukemia, ..
  67. Bartholomeeusen K, Christ F, Hendrix J, Rain J, Emiliani S, Benarous R, et al. Lens epithelium-derived growth factor/p75 interacts with the transposase-derived DDE domain of PogZ. J Biol Chem. 2009;284:11467-77 pubmed publisher
    Lens epithelium-derived growth factor/p75 (LEDGF/p75) is a prominent cellular interaction partner of human immunodeficiency virus-1 (HIV-1) integrase, tethering the preintegration complex to the host chromosome...
  68. Ge H, Si Y, Wolffe A. A novel transcriptional coactivator, p52, functionally interacts with the essential splicing factor ASF/SF2. Mol Cell. 1998;2:751-9 pubmed
    ..Here, we describe that a novel transcriptional coactivator, p52, interacts not only with transcriptional activators and general transcription factors to enhance activated ..
  69. Maertens G, Vercammen J, Debyser Z, Engelborghs Y. Measuring protein-protein interactions inside living cells using single color fluorescence correlation spectroscopy. Application to human immunodeficiency virus type 1 integrase and LEDGF/p75. FASEB J. 2005;19:1039-41 pubmed
    ..integrase (IN) with a cellular protein, lens epithelium-derived growth factor/transcription co-activator p75 (LEDGF/p75)...
  70. Llano M, Saenz D, Meehan A, Wongthida P, Peretz M, Walker W, et al. An essential role for LEDGF/p75 in HIV integration. Science. 2006;314:461-4 pubmed
    ..protein approaches to show that the cellular transcriptional coactivator lens epithelium-derived growth factor (LEDGF)/p75 (p75) is an essential HIV integration cofactor...
  71. Tsiang M, Jones G, Hung M, Samuel D, Novikov N, Mukund S, et al. Dithiothreitol causes HIV-1 integrase dimer dissociation while agents interacting with the integrase dimer interface promote dimer formation. Biochemistry. 2011;50:1567-81 pubmed publisher
    ..Peptides derived from the IN binding domain (IBD) of lens epithelium derived growth factor/transcriptional coactivator p75 (LEDGF), a cellular cofactor that interacts with the IN dimer ..
  72. Zamborlini A, Coiffic A, Beauclair G, Delelis O, Paris J, Koh Y, et al. Impairment of human immunodeficiency virus type-1 integrase SUMOylation correlates with an early replication defect. J Biol Chem. 2011;286:21013-22 pubmed publisher
    ..Because SUMOylation-defective IN mutants retained WT catalytic activity, we hypothesize that SUMOylation might regulate the affinity of IN for co-factors, contributing to efficient HIV-1 replication. ..
  73. Daugaard M, Baude A, Fugger K, Povlsen L, Beck H, Sørensen C, et al. LEDGF (p75) promotes DNA-end resection and homologous recombination. Nat Struct Mol Biol. 2012;19:803-10 pubmed publisher
    Lens epithelium-derived growth factor p75 splice variant (LEDGF) is a chromatin-binding protein known for its antiapoptotic activity and ability to direct human immunodeficiency virus into active transcription units...
  74. Schrijvers R, Vets S, De Rijck J, Malani N, Bushman F, Debyser Z, et al. HRP-2 determines HIV-1 integration site selection in LEDGF/p75 depleted cells. Retrovirology. 2012;9:84 pubmed publisher
    Lens epithelium-derived growth factor (LEDGF/p75) is a cellular co-factor of HIV-1 integrase (IN) that tethers the viral pre-integration complex to the host cell chromatin and determines the genome wide integration site distribution ..
  75. Emiliani S, Mousnier A, Busschots K, Maroun M, Van Maele B, Tempé D, et al. Integrase mutants defective for interaction with LEDGF/p75 are impaired in chromosome tethering and HIV-1 replication. J Biol Chem. 2005;280:25517-23 pubmed
    ..We have recently described that the transcriptional co-activator LEDGF/p75 strongly interacts with HIV-1 integrase...
  76. Rahman S, Lu R, Vandegraaff N, Cherepanov P, Engelman A. Structure-based mutagenesis of the integrase-LEDGF/p75 interface uncouples a strict correlation between in vitro protein binding and HIV-1 fitness. Virology. 2007;357:79-90 pubmed
    b>LEDGF/p75 binding-defective IN mutant viruses were previously characterized as replication-defective, yet RNAi did not reveal an essential role for the host factor in HIV-1 replication...
  77. Vandegraaff N, Engelman A. Molecular mechanisms of HIV integration and therapeutic intervention. Expert Rev Mol Med. 2007;9:1-19 pubmed
    ..The progress towards developing integrase inhibitors for their use in the clinic is also reviewed. ..
  78. Michel F, Crucifix C, Granger F, Eiler S, Mouscadet J, Korolev S, et al. Structural basis for HIV-1 DNA integration in the human genome, role of the LEDGF/P75 cofactor. EMBO J. 2009;28:980-91 pubmed publisher
    ..a stable and functional complex between the wild-type full-length integrase (IN) and the cellular cofactor LEDGF/p75 that shows enhanced in vitro integration activity compared with the integrase alone...
  79. Hare S, Di Nunzio F, Labeja A, Wang J, Engelman A, Cherepanov P. Structural basis for functional tetramerization of lentiviral integrase. PLoS Pathog. 2009;5:e1000515 pubmed publisher
    ..of maedi-visna virus IN in complex with the IN binding domain of the common lentiviral integration co-factor LEDGF. The structures reveal that the dimer-of-dimers architecture of the IN tetramer is stabilized by swapping N-..
  80. Pradeepa M, Sutherland H, Ule J, Grimes G, Bickmore W. Psip1/Ledgf p52 binds methylated histone H3K36 and splicing factors and contributes to the regulation of alternative splicing. PLoS Genet. 2012;8:e1002717 pubmed publisher
    ..Here we demonstrate that the PWWP domain of the chromatin-associated protein Psip1/Ledgf can specifically recognize tri-methylated H3K36 and that, like this histone modification, the Psip1 short (p52) ..
  81. Hu G, Li X, Zhang X, Li Y, Ma L, Yang L, et al. Discovery of inhibitors to block interactions of HIV-1 integrase with human LEDGF/p75 via structure-based virtual screening and bioassays. J Med Chem. 2012;55:10108-17 pubmed publisher
    This study aims to identify inhibitors that bind at the interface of HIV-1 integrase (IN) and human LEDGF/p75, which represents a novel target for anti-HIV therapy. To date, only a few such inhibitors have been reported...
  82. Llano M, Delgado S, Vanegas M, Poeschla E. Lens epithelium-derived growth factor/p75 prevents proteasomal degradation of HIV-1 integrase. J Biol Chem. 2004;279:55570-7 pubmed
    The transcriptional coactivator lens epithelium-derived growth factor (LEDGF)/p75 acts as a chromatin tethering factor for human immunodeficiency virus type 1 (HIV-1) integrase protein, determining its nuclear localization and its tight ..
  83. Hayouka Z, Rosenbluh J, Levin A, Loya S, Lebendiker M, Veprintsev D, et al. Inhibiting HIV-1 integrase by shifting its oligomerization equilibrium. Proc Natl Acad Sci U S A. 2007;104:8316-21 pubmed
    ..the inhibition of the HIV-1 integrase (IN) protein by using peptides derived from its cellular-binding protein, LEDGF/p75, which specifically inhibit IN activity by a noncompetitive mechanism...
  84. Ferris A, Wu X, Hughes C, Stewart C, Smith S, Milne T, et al. Lens epithelium-derived growth factor fusion proteins redirect HIV-1 DNA integration. Proc Natl Acad Sci U S A. 2010;107:3135-40 pubmed publisher
    Lens epithelium-derived growth factor (LEDGF) fusion proteins can direct HIV-1 DNA integration to novel sites in the host genome. The C terminus of LEDGF contains an integrase binding domain (IBD), and the N terminus binds chromatin...
  85. Le Rouzic E, Bonnard D, Chasset S, Bruneau J, Chevreuil F, Le Strat F, et al. Dual inhibition of HIV-1 replication by integrase-LEDGF allosteric inhibitors is predominant at the post-integration stage. Retrovirology. 2013;10:144 pubmed publisher
    b>LEDGF/p75 (LEDGF) is the main cellular cofactor of HIV-1 integrase (IN). It acts as a tethering factor for IN, and targets the integration of HIV in actively transcribed gene regions of chromatin...
  86. Maertens G, Cherepanov P, Pluymers W, Busschots K, De Clercq E, Debyser Z, et al. LEDGF/p75 is essential for nuclear and chromosomal targeting of HIV-1 integrase in human cells. J Biol Chem. 2003;278:33528-39 pubmed
    ..forms a specific nuclear complex with human lens epithelium-derived growth factor/transcription co-activator p75 (LEDGF/p75) protein...
  87. Maertens G, Cherepanov P, Engelman A. Transcriptional co-activator p75 binds and tethers the Myc-interacting protein JPO2 to chromatin. J Cell Sci. 2006;119:2563-71 pubmed
    Transcriptional co-activator p75 is implicated in human cancer, autoimmunity and replication of human immunodeficiency virus type 1 (HIV-1) as a dominant integrase-interacting protein...
  88. Hare S, Shun M, Gupta S, Valkov E, Engelman A, Cherepanov P. A novel co-crystal structure affords the design of gain-of-function lentiviral integrase mutants in the presence of modified PSIP1/LEDGF/p75. PLoS Pathog. 2009;5:e1000259 pubmed publisher
    b>Lens epithelium derived growth factor (LEDGF), also known as PC4 and SFRS1 interacting protein 1 (PSIP1) and transcriptional co-activator p75, is the cellular binding partner of lentiviral integrase (IN) proteins...
  89. Mediavilla Varela M, Pacheco F, Almaguel F, Perez J, Sahakian E, Daniels T, et al. Docetaxel-induced prostate cancer cell death involves concomitant activation of caspase and lysosomal pathways and is attenuated by LEDGF/p75. Mol Cancer. 2009;8:68 pubmed publisher
    ..Ectopic expression of lens epithelium-derived growth factor p75 (LEDGF/p75), a stress survival autoantigen and transcription co-activator, attenuated docetaxel-induced lysosomal ..
  90. Cherepanov P. LEDGF/p75 interacts with divergent lentiviral integrases and modulates their enzymatic activity in vitro. Nucleic Acids Res. 2007;35:113-24 pubmed publisher
    Transcriptional co-activator LEDGF/p75 is the major cellular interactor of HIV-1 integrase (IN), critical to efficient viral replication...
  91. Pandey K, Sinha S, Grandgenett D. Transcriptional coactivator LEDGF/p75 modulates human immunodeficiency virus type 1 integrase-mediated concerted integration. J Virol. 2007;81:3969-79 pubmed
    Human transcriptional coactivator p75/lens epithelium-derived growth factor (LEDGF) binds human immunodeficiency virus type 1 (HIV-1) integrase (IN)...
  92. Meehan A, Poeschla E. Chromatin tethering and retroviral integration: recent discoveries and parallels with DNA viruses. Biochim Biophys Acta. 2010;1799:182-91 pubmed publisher
    ..Lens epithelium-derived growth factor (LEDGF/p75) is a ubiquitously expressed nuclear protein that binds to lentiviral IN protein dimers at its carboxyl ..