Affinage

Showing PSIP1 — LEDGF is a alias.

PSIP1

PC4 and SFRS1-interacting protein · UniProt O75475

Length
530 aa
Mass
60.1 kDa
Annotated
2026-06-10
100 papers in source corpus 44 papers cited in narrative 44 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PSIP1 (LEDGF/p75) is a chromatin-associated adaptor that tethers diverse protein cargoes to transcriptionally active genomic regions, reading the H3K36me2/3 mark through its N-terminal PWWP domain and engaging partners through its C-terminal integrase-binding domain (IBD) (PMID:22615581, PMID:23396443, PMID:25082813). The PWWP domain binds H3K36me3-containing nucleosomes with nanomolar affinity via a bipartite mechanism, simultaneously contacting the methylated histone tail through a hydrophobic cavity and nucleosomal DNA through an adjacent basic surface, an interaction enhanced ~10,000-fold over peptide alone (PMID:23396443, PMID:23656834); in living cells this supports a 'scan-and-lock' mode of chromatin engagement in which the PWWP domain locks complexes onto chromatin (PMID:20974633). Through its IBD, PSIP1 binds HIV-1 integrase, MLL, JPO2, PogZ, and the Cdc7-ASK kinase in a mutually exclusive manner using a shared interface (PMID:17669426, PMID:19864417, PMID:25082813). PSIP1 is the principal cellular cofactor directing HIV-1 integration: it stabilizes and organizes an active integrase tetramer, stimulates strand transfer activity, tethers preintegration complexes to transcription units, and dictates integration site selection — a function shown to be portable, since swapping its chromatin-binding domain for the heterochromatin reader CBX1 redirects integration toward heterochromatin (PMID:12407101, PMID:17639082, PMID:18801737, PMID:20195265, PMID:23593299). Beyond viral integration, PSIP1 functions broadly in genome regulation: it tethers CtIP to DNA double-strand breaks to promote homologous-recombination repair (PMID:22773103), suppresses genome-wide R-loop accumulation at promoters in concert with PARP1 such that its loss sensitizes cancer cells to PARP inhibitors (PMID:38191578), and facilitates RNA Pol II transcription elongation past nucleosomes (PMID:31616795). Its short p52 isoform associates with SRSF1 and other splicing factors at H3K36me3-marked active genes to regulate alternative splicing (PMID:22615581, PMID:26545813). Through the IBD it recruits MLL to Hox target genes, and PSIP1 loss reduces MLL occupancy and impairs MLL-fusion leukemogenesis; correspondingly, Psip1-null mice show homeotic skeletal transformations consistent with disrupted Hox regulation (PMID:16980622, PMID:25082813, PMID:29084774). PSIP1 also binds heat-shock and stress-response promoter elements to transactivate stress and survival genes (PMID:11350077, PMID:15238362).

Mechanistic history

Synthesis pass · year-by-year structured walk · 31 steps
  1. 2000 High

    Establishing that the PSIP1 locus generates two isoforms by alternative splicing defined the molecular basis for the distinct activities later assigned to p75 and p52.

    Evidence gene cloning, exon/intron mapping, and RT-PCR of the chromosome 9p22.2 locus

    PMID:10721720

    Open questions at the time
    • Did not assign function to either isoform
    • No protein structure or domain function defined
  2. 2002 High

    Identifying LEDGF/p75 as a stable interactor of HIV-1 integrase that enhances strand transfer activity defined the protein's role as a candidate cellular cofactor for integration.

    Evidence Co-IP from nuclear extracts, gel filtration, in vitro strand transfer assay, and co-localization microscopy

    PMID:12407101

    Open questions at the time
    • Did not establish requirement for viral replication
    • Domain responsible for IN binding not yet mapped
  3. 2003 High

    RNAi depletion showed LEDGF/p75 is required for nuclear and chromosomal targeting of integrase and that p52 does not bind IN, establishing isoform-specific cofactor function.

    Evidence RNAi knockdown with live-cell imaging and in vitro pull-down of isoforms

    PMID:12796494

    Open questions at the time
    • Did not distinguish tethering from import requirement
    • Functional consequence for replication not yet shown
  4. 2004 High

    Mapping the NLS and demonstrating Ran/importin-dependent nuclear import explained how LEDGF/p75 carries integrase into the nucleus.

    Evidence deletion/mutagenesis with semipermeabilized-cell nuclear import assay and GFP fusions

    PMID:15163664

    Open questions at the time
    • Did not separate import role from chromatin-tethering role
  5. 2005 High

    Showing the IN-LEDGF interaction is lentivirus-specific and essential for viral replication, separable from IN enzymatic activity, defined the interaction as a discrete druggable cofactor function.

    Evidence isoform/integrase-specific pull-downs, FCS DNA-binding, two-hybrid mutagenesis, and viral replication assays

    PMID:15749713 PMID:15855167

    Open questions at the time
    • Atomic basis of the interface not yet resolved
    • Chromatin-tethering step not yet directly demonstrated
  6. 2006 High

    Mapping the IN-binding residues on integrase and the conserved D366 contact on LEDGF, plus showing in vivo Hox/developmental phenotypes in knockout mice, jointly defined both the viral interface and an endogenous developmental role.

    Evidence systematic mutagenesis across lentiviral integrases, in vitro strand transfer assays, and gene-trap knockout mouse phenotyping

    PMID:16980622 PMID:17137594 PMID:17158150

    Open questions at the time
    • Mechanistic link between PSIP1 and Hox gene regulation not yet defined
    • Chromatin-reading domain function still unresolved
  7. 2006 High

    Live-cell mutagenesis showed chromatin association is driven by a tripartite NLS/AT-hook element with a modulatory role for the PWWP domain, refining how LEDGF docks on chromatin.

    Evidence SPR/EMSA DNA binding with EGFP-fusion localization in interphase and mitotic cells

    PMID:16549878

    Open questions at the time
    • Did not identify the histone mark recognized by PWWP
    • Relative contribution of each element to integration not yet quantified
  8. 2007 High

    Genetic knockout showed LEDGF acts downstream of PIC formation to bias integration into transcription units, establishing the tethering model of integration site selection.

    Evidence LEDGF-null cells with HIV-1 integration site mapping and PIC strand transfer assays

    PMID:17639082

    Open questions at the time
    • Chromatin feature read by LEDGF to define targets not yet identified
  9. 2007 High

    Defining JPO2 as a cellular IBD ligand competing with integrase introduced the principle that the IBD engages multiple partners through one mutually exclusive site.

    Evidence two-hybrid, AlphaScreen, reciprocal Co-IP, and competition assays

    PMID:17669426

    Open questions at the time
    • Cellular function of the JPO2 interaction unresolved
  10. 2008 High

    Demonstrating that the PWWP domain binds nucleosomes directly and is the primary determinant for stimulating integration into chromatinized templates connected chromatin reading to cofactor function.

    Evidence systematic PWWP mutagenesis, GST pull-down of nucleosomes, and in vitro integration into polynucleosome templates

    PMID:18174227 PMID:18799576

    Open questions at the time
    • Specific histone modification recognized not yet identified
  11. 2008 High

    Showing LEDGF stabilizes IN-IN contacts and promotes integrase tetramerization revealed it functions as an allosteric organizer of the active integrase multimer, not merely a tether.

    Evidence MS protein footprinting, molecular modeling, and enzymatic assays of full-length IN-LEDGF

    PMID:18801737

    Open questions at the time
    • Stoichiometry of the assembled complex not yet defined
  12. 2009 High

    Discovery of the Cdc7-ASK interaction and LEDGF-stimulated MCM2 phosphorylation revealed a cellular role in DNA replication kinase activation via the IBD.

    Evidence endogenous reciprocal Co-IP, in vitro kinase assays with MCM2, and phosphorylation-site mapping

    PMID:19864417

    Open questions at the time
    • In vivo importance for replication timing not established
  13. 2009 High

    The IN NTD+CCD-IBD crystal structure defined the charge-charge basis of lentiviral specificity, providing the structural template for understanding the interaction and its inhibition.

    Evidence X-ray crystallography with mutagenesis and concerted integration/infectivity assays

    PMID:19132083

    Open questions at the time
    • Structure of the full-length IN-LEDGF-DNA assembly not yet resolved
  14. 2009 Medium

    ChIP linking LEDGF/p75 to the VEGF-C promoter under hormonal control extended its function to transcriptional regulation of lymphangiogenesis genes.

    Evidence ChIP, siRNA knockdown, and promoter-reporter assays in ovarian cancer cells

    PMID:19934313

    Open questions at the time
    • Direct DNA-binding versus tethered recruitment at this promoter not distinguished
    • Single lab
  15. 2010 High

    Genome-wide chromatin profiling and the scan-and-lock kinetic model defined where and how LEDGF engages active chromatin, and that integrase binding markedly increases its chromatin affinity.

    Evidence DamID profiling and FRAP/FCS live-cell kinetics with domain mutants

    PMID:20484370 PMID:20974633

    Open questions at the time
    • Why only a subset of LEDGF-bound sites support integration unresolved
  16. 2010 High

    Replacing the chromatin-binding domain with CBX1 to redirect integration to heterochromatin provided causal proof that the tethering domain dictates integration site selection.

    Evidence chimeric protein engineering with lentiviral integration site sequencing

    PMID:20195265

    Open questions at the time
    • Did not address endogenous cellular consequences of retargeting
  17. 2011 High

    FRET order-of-addition and in vitro tethering assays defined how LEDGF shapes integrase conformation and stimulates IN-DNA binding, sharpening the mechanistic model of complex assembly.

    Evidence FRET of IN assembly and AlphaScreen IN-DNA tethering assays with domain mutants

    PMID:21763490 PMID:21771857

    Open questions at the time
    • Medium-confidence quantitation for the tethering assay; single lab
  18. 2011 Medium

    Identifying a supercoiled-DNA recognition domain that localizes to transcriptionally active regions added a DNA-topology preference to LEDGF chromatin targeting.

    Evidence recombinant fragment supercoiled-DNA binding and EGFP-SRD localization with immunostaining

    PMID:21345933

    Open questions at the time
    • Relationship of SRD to PWWP-based targeting not integrated
    • Single lab
  19. 2012 High

    Demonstrating damage-dependent recruitment of CtIP to DSBs via the PWWP domain established a direct role for PSIP1 in homologous-recombination repair.

    Evidence RNAi depletion, CtIP recruitment and DNA-end resection assays, and damage-dependent Co-IP

    PMID:22773103

    Open questions at the time
    • Whether the same PWWP-chromatin contacts mediate both integration and repair tethering not directly compared
  20. 2012 Medium

    Identifying MeCP2 as an N-terminal-domain partner shared by both isoforms expanded the transcriptional-regulator interactome of PSIP1.

    Evidence protein arrays, AlphaScreen, Co-IP, confocal co-localization, and Hsp27 reporter assays

    PMID:22275515

    Open questions at the time
    • Cell-context dependence of the functional effect unresolved
    • Single lab
  21. 2012 High

    Establishing that the PWWP domain specifically reads H3K36me3 and that p52 couples this mark to SRSF1 connected chromatin reading to alternative splicing regulation.

    Evidence PWWP H3K36me3 binding, p52-splicing-factor Co-IP, ChIP, and splicing analysis in Psip1 mutant cells

    PMID:22615581

    Open questions at the time
    • Genome-wide breadth of splicing control not yet quantified
  22. 2013 High

    NMR structures resolved the bipartite PWWP mechanism — cooperative histone-tail and nucleosomal-DNA contacts producing nanomolar, ~10,000-fold-enhanced nucleosome binding — explaining high-affinity targeting to H3K36me3 chromatin.

    Evidence NMR solution structure, mutagenesis, and thermodynamic binding to reconstituted mononucleosomes

    PMID:23396443 PMID:23656834

    Open questions at the time
    • How partner binding at the IBD couples to this PWWP affinity not structurally resolved
  23. 2013 High

    Defining the IN4:LEDGF2:INI1-IBD2:DNA2 stoichiometry by cryo-EM and MS established the architecture of the LEDGF-stabilized active integration intasome.

    Evidence reconstitution, MS stoichiometry, FCS, integration assays, and cryo-EM

    PMID:23593299

    Open questions at the time
    • High-resolution atomic model of the full assembly not obtained
  24. 2014 High

    Mapping the MLL interface to the same mutually exclusive IBD site and showing its mutation impairs MLL-AF9 transformation linked the cofactor function to leukemogenesis.

    Evidence NMR interface mapping, mutagenesis, AlphaScreen competition, and colony-forming assays

    PMID:25082813

    Open questions at the time
    • In vivo leukemia dependence not yet tested in this study
  25. 2014 High

    Complete TALEN knockout confirmed PSIP1's requirement for HIV integration while showing particle assembly and ALLINI action are LEDGF-independent, delimiting the cofactor's mechanistic scope.

    Evidence whole-gene and IBD-exon TALEN knockouts with replication, infectivity, and assembly assays

    PMID:24942577

    Open questions at the time
    • Residual integration in knockout cells not fully explained
  26. 2015 High

    Affinity purification and RNA-seq in knockout cells established PSIP1 as a broad regulator of alternative splicing and linked intron density to LEDGF-dependent integration patterns.

    Evidence affinity purification of splicing factors and RNA-seq plus >1M integration-site mapping in KO cells

    PMID:26545813

    Open questions at the time
    • Direct versus indirect contribution to each splicing event not resolved
  27. 2017 High

    Conditional knockout and ChIP showed PSIP1 sustains MLL occupancy at Hox genes and is required for MLL-fusion leukemia initiation but dispensable for normal hematopoiesis, defining a context-specific oncogenic dependency.

    Evidence conditional KO mouse, Hox expression, MLL ChIP, and in vitro/in vivo leukemia models

    PMID:29084774

    Open questions at the time
    • Molecular basis of leukemia-specific dependence not fully defined
  28. 2017 Medium

    Additional studies tied p52 to lncRNA Hottip-dependent Hoxa activation and p75 to RNA Pol II recruitment at cell-cycle gene promoters in breast cancer, broadening PSIP1's transcriptional roles.

    Evidence Hottip knockdown/knockout and Mll1 ChIP; PSIP1-Pol II Co-IP, promoter ChIP, and tumorigenicity assays

    PMID:28384324 PMID:28633434

    Open questions at the time
    • Single-lab findings
    • Mechanistic link between Pol II recruitment and tumorigenicity not fully resolved
  29. 2019 Medium

    Showing PWWP-mediated H3K36me2/3 binding supports RNA Pol II elongation past nucleosomes defined a FACT-like role in transcription elongation.

    Evidence genome-wide co-localization with H3K36me2/3 and RNAPII ChIP-seq (primary focus on paralog HDGF2)

    PMID:31616795

    Open questions at the time
    • Direct elongation defect upon LEDGF/p75 loss not separately demonstrated
    • Mechanism inferred largely from HDGF2
  30. 2020 High

    Dissecting PSIP1-dependent competition between PAF1 and the CKII-activated MLL1/SEC at the provirus explained how LEDGF toggles HIV transcription between latency and activation.

    Evidence reciprocal Co-IP, ChIP at the provirus, and CKII inhibition in latency-reversal assays

    PMID:32426500

    Open questions at the time
    • Whether the same switch operates at host genes not addressed
  31. 2024 High

    Defining PSIP1's interaction with PARP1 and R-loop homeostasis factors revealed it suppresses promoter R-loops and transcription-replication conflicts, with loss imposing PARP-inhibitor sensitivity.

    Evidence Co-IP, DRIP-seq, γ-H2AX ChIP-seq, 53BP1/RAD51 foci, and PARP-inhibitor viability assays in PSIP1-depleted cells

    PMID:38191578

    Open questions at the time
    • Mechanism by which PSIP1 resolves R-loops not established
    • Relationship to its HR/CtIP function not integrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PSIP1 coordinates its single chromatin-reading domain and one mutually exclusive IBD across its many roles — integration, HR repair, splicing, elongation, R-loop control, and MLL-driven transcription — into context-specific outcomes remains unresolved.
  • No unified model of how partner selection at the IBD is regulated in cells
  • Whether PWWP chromatin reading is rate-limiting for each function is untested
  • High-resolution structures of most non-viral complexes are lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 4 GO:0060090 molecular adaptor activity 4 GO:0042393 histone binding 3 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 3
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 2 GO:0005654 nucleoplasm 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-4839726 Chromatin organization 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-73894 DNA Repair 2 R-HSA-8953854 Metabolism of RNA 2
Partners
CDC7CTIPHIV-1 INTEGRASEJPO2MLLPARP1POGZSRSF1
Complex memberships
HIV-1 preintegration complex (IN tetramer–LEDGF dimer)MLL complexPAF1 complex (at HIV provirus)

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 HIV-1 integrase (IN) forms stable tetramers in human cell nuclei and associates with LEDGF/p75 to form a larger ~61 Å complex; recombinant LEDGF/p75 robustly enhanced strand transfer activity of HIV-1 IN in vitro, and IN co-localizes with LEDGF/p75 in the nucleus. FLAG-tag co-immunoprecipitation from nuclear extracts, gel filtration, in vitro strand transfer assay, co-localization by fluorescence microscopy The Journal of biological chemistry High 12407101
2003 LEDGF/p75 is essential for nuclear localization and chromosomal targeting of HIV-1 integrase; knockdown of endogenous LEDGF/p75 by RNAi abolished nuclear/chromosomal localization of IN. The alternative splice variant p52 did not interact with HIV-1 IN in vitro or in living cells. RNAi knockdown, EGFP/HcRed1 live-cell fluorescence imaging, in vitro pull-down, domain deletion/mutant analysis The Journal of biological chemistry High 12796494
2000 LEDGF/p75 and p52 are derived from a single gene (PSIP1) by alternative splicing; exons 1–15 encode p75 and exons 1–9 plus part of intron 9 encode p52; the gene is located on chromosome 9p22.2. Gene cloning, sequencing, exon/intron mapping, RT-PCR expression analysis Gene High 10721720
2001 LEDGF binds to heat shock element (HSE; nGAAn) and stress-related regulatory element (STRE; A/TGGGGA/T) in the promoters of stress-related genes (Hsp27 and αB-crystallin) to activate their transcription. DNA-binding assay, transcriptional reporter assay, promoter element deletion/mutation Biochemical and biophysical research communications Medium 11350077
2001 LEDGF/p75 is distributed diffusely in the nucleoplasm during G1 and attaches to condensed chromatin during G2/M (mitosis), whereas p52 localizes to the nuclear periphery in G1 and forms speckles at S-phase, indicating distinct nuclear compartments and functions. Live-cell fluorescence imaging of GFP-tagged proteins across cell cycle stages in CHO-K1, MCDK, and NRK cells Cell and tissue research Medium 11512661
2004 LEDGF/p75 nuclear import is GTP-, Ran-, importin-α/β-, and energy-dependent; the functional NLS was mapped to residues 148–156 (GRKRKAEKQ); a single amino acid change in the NLS excluded LEDGF/p75 from the nucleus and abolished nuclear import of HIV-1 integrase. Deletion analysis, site-directed mutagenesis, semipermeabilized cell nuclear import assay, GFP fusion constructs in live cells, β-galactosidase NLS transfer assay The Journal of biological chemistry High 15163664
2005 LEDGF/p75 interacts with HIV-1, HIV-2, and feline immunodeficiency virus integrase but not with non-lentiviral integrases (HTLV-2, MoMLV, RSV); LEDGF/p75 strongly promoted binding of HIV-1 and HIV-2 IN to DNA, an effect specific to the p75 isoform and not seen with p52. Pull-down binding assay, fluorescence correlation spectroscopy for DNA-binding measurements, isoform-specific comparisons The Journal of biological chemistry High 15749713
2005 Interaction of HIV-1 integrase with LEDGF/p75 is essential for viral replication and chromosomal tethering of IN; a single integrase mutation that disrupts LEDGF/p75 interaction (without reducing enzymatic activity) results in defective HIV-1 replication. Two-hybrid assays, random and directed mutagenesis, viral replication assays The Journal of biological chemistry High 15855167
2005 Both the IN-binding and DNA-binding activities of LEDGF/p75 contribute to functional reconstitution of HIV-1 preintegration complex (PIC) in vitro; recombinant LEDGF/p75 efficiently reconstitutes high-salt-disrupted PIC activity. In vitro PIC reconstitution assay with recombinant proteins, mutational analysis of LEDGF/p75 domains Virology Medium 16337983
2006 LEDGF/p75 chromatin association in living cells is mediated by a tripartite element comprising the NLS and two AT-hook motifs (residues 146–197); the PWWP domain is not required for binding condensed mitotic chromosomes but subtly affects interphase nucleoplasmic distribution; neither DNA-binding-deficient LEDGF/p75 mutants nor the AT-hook mutant lost chromatin binding unless combined with NLS mutations or PWWP deletion. SPR and EMSA for DNA binding, EGFP fusion localization in interphase and mitotic cells, domain deletion and AT-hook mutagenesis Nucleic acids research High 16549878
2006 LEDGF/p75 interacts with and stimulates strand transfer activity of all lentiviral integrases tested (BIV, MVV, EIAV) but not non-lentiviral integrases; mutation D366N in LEDGF ablates interaction with all lentiviral INs, suggesting a conserved recognition mechanism; in the presence of LEDGF, EIAV IN almost exclusively catalyzes concerted integration. Pull-down, yeast two-hybrid, in vitro strand transfer assay with divergent lentiviral INs, site-directed mutagenesis Nucleic acids research High 17158150
2006 Psip1/Ledgf knockout mice exhibit perinatal mortality, homeotic skeletal transformations, motor/behavioral defects, and craniofacial abnormalities, implicating PSIP1 in Hox gene expression regulation in vivo. Gene trap mutagenesis in mouse ES cells, homozygous knockout mouse phenotypic analysis Molecular and cellular biology High 16980622
2006 The LEDGF/p75-binding site on HIV-1 integrase maps to two regions: residues around W131/W132 and residues I161–E170; mutations at W131, I161, R166, Q168, and E170 impair LEDGF/p75 interaction but retain IN enzymatic activity; the W131A mutation reduces HIV-1 replication. Yeast two-hybrid, in vitro binding/pull-down, IN enzymatic activity assays, HIV-1 replication assays, structural comparison Journal of molecular biology High 17137594
2007 LEDGF/p75 functions downstream from HIV-1 preintegration complex formation to direct integration into transcription units; in LEDGF-null cells, HIV-1 loses its strong bias toward integrating into transcription units and instead shows increased affinity for promoter regions and CpG islands, while 3'-end processing and local target DNA sequence preference are unaffected. Genetic knockout of LEDGF, HIV-1 vector integration site mapping, quantitative PCR, in vitro strand transfer assays with PICs from knockout cells Genes & development High 17639082
2007 JPO2 binds the C-terminal integrase-binding domain (IBD) of LEDGF/p75 in a mutually exclusive manner with HIV-1 integrase; the binding mechanism differs (JPO2 continues to interact with some IN-defective LEDGF/p75 mutants like I365A, D366A, F406A); JPO2 overexpression modestly inhibits HIV-1 replication. Yeast two-hybrid, pull-down, AlphaScreen, co-immunoprecipitation, competition assays with recombinant proteins, HIV-1 replication assay Journal of molecular biology High 17669426
2008 LEDGF/p75 strongly stabilizes IN-IN subunit interactions and promotes IN tetramerization; mass spectrometric protein footprinting revealed novel intra- and inter-protein contacts in the full-length IN-LEDGF complex beyond the IBD-CCD co-crystal structure; the IN tetramer interface is important for enzymatic activities and high-affinity LEDGF binding. Mass spectrometric protein footprinting, molecular modeling, biochemical characterization of full-length IN-LEDGF interactions, enzymatic assays The Journal of biological chemistry High 18801737
2008 The PWWP domain of LEDGF/p75 is required for chromatin binding and HIV-1 infectivity; mutations at W21 or A51 (which line a hydrophobic cavity conserved among Tudor clan members) disrupt chromatin binding and virus infectivity; W21A recombinant protein is preferentially defective for enhancing integration into chromatinized (but not naked) DNA in vitro. Systematic mutagenesis of 24 PWWP residues, chromatin binding assays, HIV-1 infectivity assays, in vitro integration into chromatinized templates Journal of virology High 18799576
2008 The PWWP domain of LEDGF/p75 is required for stimulation of HIV-1 integration into reconstituted polynucleosome (chromatinized) templates; the PWWP domain binds directly to nucleosomes in GST pull-down assays; with naked DNA, full removal of N-terminal chromatin-binding elements is needed to abate cofactor function, but with polynucleosomes, PWWP domain is the primary determinant. In vitro integration assay with reconstituted polynucleosome templates, GST pull-down, domain deletion analysis Nucleic acids research High 18174227
2009 LEDGF/p75 interacts with the Cdc7-ASK (activator of S-phase kinase) heterodimer through its integrase-binding domain (IBD); the interaction requires autophosphorylation of Cdc7 and the C-terminal 50 residues of ASK; Cdc7-ASK phosphorylates LEDGF at Ser-206 (primarily during S phase); LEDGF potently stimulates Cdc7-ASK kinase activity, increasing MCM2 phosphorylation >10-fold in vitro, by relieving ASK C-terminus-mediated autoinhibition. Co-immunoprecipitation of endogenous proteins, truncation analysis, in vitro kinase assay with MCM2 substrate, phosphorylation site mapping The Journal of biological chemistry High 19864417
2009 LEDGF/p75 crystal structure (HIV-2 IN NTD+CCD in complex with LEDGF IBD) revealed charge-charge interactions between the IN N-terminal domain (NTD) and the IBD; a constellation of acidic residues on the NTD is characteristic of lentiviral INs; mutations of positively charged IBD residues severely impaired interaction with all lentiviral INs and abrogated stimulation of concerted integration and HIV-1 replication. X-ray crystallography, site-directed mutagenesis, in vitro concerted integration assay, HIV-1 infectivity assays PLoS pathogens High 19132083
2010 LEDGF/p75 is primarily bound downstream of transcription start sites of active transcription units in chromatin, co-localizing with active chromatin markers (H3/H4 acetylation, H3K4me1, RNA Pol II); not all LEDGF/p75-bound chromosomal complexes are amenable to HIV-1 integration. DamID chromatin profiling in ENCODE regions, correlation analysis with >200 genomic features including HIV-1 integration sites Nucleic acids research Medium 20484370
2010 LEDGF/p75 chromatin binding in living cells follows a 'scan-and-lock' mechanism: the protein moves in a chromatin hopping/scanning mode; the PWWP domain is necessary but not sufficient for in vivo chromatin binding; upon binding HIV-1 integrase via its IBD, LEDGF/p75 kinetics shift to 75-fold larger chromatin affinity, with PWWP domain crucial for locking the complex on chromatin. FRAP (spot- and half-nucleus), continuous photobleaching, fluorescence correlation spectroscopy, tunable focus FCS in living HeLa cells Nucleic acids research High 20974633
2010 Replacement of the LEDGF/p75 chromatin interaction domain with CBX1 (which binds H3K9me2/3 at pericentric heterochromatin) redirects lentiviral vector integration away from genes and toward heterochromatin, demonstrating that LEDGF/p75 chromatin-tethering domain determines integration site selection. Chimeric protein engineering, lentiviral vector transduction, integration site sequencing Molecular therapy High 20195265
2011 FRET analysis revealed that HIV-1 IN tetramers adopt distinct conformations in the presence of viral DNA versus LEDGF/p75; pre-formed IN-viral DNA complex conformation is unchanged upon subsequent LEDGF/p75 binding, but pre-incubation with LEDGF followed by viral DNA yields IN conformation similar to the IN-LEDGF complex. FRET monitoring of IN subunit assembly in the presence of viral DNA and LEDGF/p75, order-of-addition experiments Nucleic acids research High 21771857
2011 LEDGF/p75 tethers HIV-1 IN to DNA in vitro: LEDGF/p75 stimulates IN binding to DNA 10–30-fold in a manner requiring direct IN-LEDGF C-terminus interaction; overexpression of LEDGF C-terminus or NLS/AT-hook mutant LEDGF inhibits IN-DNA interaction. AlphaScreen assay for IN-DNA interaction, domain-deletion analysis, in vitro DNA-binding Journal of molecular biology Medium 21763490
2011 LEDGF/p75 recognizes supercoiled DNA preferentially over unconstrained DNA via a novel 'supercoiled DNA-recognition domain' (SRD) containing a K/E/D cluster; GFP-SRD in cells localizes to transcriptionally active regions (H3K4me3, Br-UTP incorporation); deletion of SRD abolishes this localization. Recombinant protein fragments with in vitro supercoiled DNA-binding assays, EGFP-tagged localization with immunostaining in live cells Nucleic acids research Medium 21345933
2012 LEDGF/p75 promotes DNA double-strand break repair by homologous recombination; LEDGF depletion impairs recruitment of CtIP to DNA DSBs and CtIP-dependent DNA-end resection; LEDGF binds CtIP in a DNA damage-dependent manner through its PWWP domain interaction with chromatin, tethering CtIP to active chromatin near DSBs. RNAi depletion, CtIP recruitment assay at DSBs, DNA-end resection assay, co-immunoprecipitation (damage-dependent), chromatin binding Nature structural & molecular biology High 22773103
2012 The PWWP domain of Psip1/Ledgf specifically recognizes trimethylated H3K36; the p52 (short) isoform, enriched at active genes like H3K36me3, co-localizes and interacts with Srsf1 and other mRNA processing proteins; in Psip1 mutant cells, H3K36me3-associated Srsf1 is reduced and alternative splicing of specific genes is altered. PWWP domain H3K36me3 binding assay, co-immunoprecipitation of p52 with splicing factors, ChIP, splicing analysis in Psip1 mutant cells PLoS genetics High 22615581
2013 The LEDGF PWWP domain binds H3K36me3-containing mononucleosomes with nanomolar affinity via two distinct functional interfaces: a hydrophobic cavity that selectively contacts H3K36me3 peptide, and an adjacent basic surface that non-specifically binds DNA; cooperative binding to both methylated histone tail and nucleosomal DNA is essential for high-affinity chromatin binding. NMR solution structure of PWWP domain, binding to H3K36me3 peptide and DNA monitored by NMR, affinity measurements to native and reconstituted mononucleosomes, mutational analysis, proteomic experiments Nucleic acids research High 23396443
2013 PSIP1-PWWP binds H3K36-methylated nucleosomes through simultaneous bipartite interactions with the methylated histone tail and nucleosomal DNA; binding is enhanced ~10,000-fold compared to methylated peptide alone; this bipartite mechanism was structurally characterized by NMR and mutational analysis. NMR spectroscopy, extensive mutational analysis, computational approaches, thermodynamic binding measurements Epigenetics & chromatin High 23656834
2013 In the HIV-1 preintegration complex, LEDGF/p75 organizes and stabilizes an active integrase tetramer (stoichiometry IN4:LEDGF2:INI1-IBD2:DNA2); INI1-IBD occupies the cellular DNA binding site of the IN-LEDGF complex and constrains integrase in a stable conformation. Stable complex reconstitution, mass spectrometry stoichiometry determination, fluorescence correlation spectroscopy, functional integration assay, cryo-electron microscopy PloS one High 23593299
2014 NMR spectroscopy identified an additional LEDGF/p75-MLL interface overlapping with the HIV-1 integrase, PogZ, and JPO2 binding site on the IBD; binding of MLL, HIV-1 IN, PogZ, and JPO2 to LEDGF/p75 is mutually exclusive; the MLL interaction is primarily sustained by two aromatic residues (F148 and F151 of MLL); mutation of this interface impairs MLL-AF9+ leukemic cell transformation. NMR spectroscopy for interface mapping, mutational analysis, AlphaScreen competition assays, colony-forming assays Cancer research High 25082813
2014 Complete TALEN-mediated knockout of PSIP1 in human cells severely impairs HIV-1 spreading replication and single-cycle integration; HIV-1 particle assembly and the main ALLINI (allosteric integrase inhibitor) mechanism are LEDGF/p75-independent. TALEN-mediated gene knockout (whole-gene deletion and IBD exon deletion), HIV-1 replication and single-cycle infectivity assays, virus assembly assays Journal of virology High 24942577
2015 LEDGF/p75 is associated with multiple mRNA splicing factors by affinity purification; LEDGF/p75 (or its IBD) contributes to splicing patterns in approximately half of transcription units with alternative isoforms; HIV-1 integration density in transcription units correlates with intron number in a LEDGF-dependent manner. Affinity purification of LEDGF/p75-associated splicing factors, RNA-seq analysis of LEDGF/p75 or IBD knockout HEK293T cells, HIV-1 integration site sequencing (>1 million sites), multivariate analysis Genes & development High 26545813
2017 Conditional Psip1 knockout in hematopoietic cells decreases Hox gene expression, reduces MLL occupancy at MLL target genes, and impairs MLL-fusion-mediated leukemia initiation in vitro and in vivo, but is dispensable for steady-state hematopoiesis. Conditional knockout mouse model, Hox gene expression analysis, ChIP for MLL occupancy, in vitro colony-forming assays, in vivo bone marrow transplant leukemia model Blood High 29084774
2017 PSIP1/p75 interacts with RNA polymerase II and facilitates its association with promoters of cell cycle genes, thereby regulating their transcription and promoting triple-negative breast cancer tumorigenicity. Co-immunoprecipitation of PSIP1 with RNA Pol II, ChIP for RNA Pol II at promoters in PSIP1-depleted cells, gene expression analysis, tumorigenicity assays Carcinogenesis Medium 28633434
2017 Psip1/p52 (short isoform) specifically regulates expression of lncRNA Hottip at the Hoxa locus; Hottip is required for activation of posterior Hoxa genes (Hoxa13, Hoxa10/11) and for retaining Mll1 at the 5' end of Hoxa; the Hottip RNA molecule itself (not just its transcription) is required for Hox gene activation. Knockdown and knockout approaches, Hottip overexpression, premature transcription termination engineering, Mll1 ChIP PLoS genetics Medium 28384324
2019 LEDGF/p75 (and HDGF2) bind H3K36me2 and H3K36me3 via their PWWP domains and, like FACT, facilitate RNA Pol II transcription elongation past nucleosome barriers; in differentiated myotubes, HDGF2 depletion causes paused RNAPII accumulation within transcribed regions of target genes, indicating a defect in early elongation. Genome-wide co-localization with H3K36me2/3, HDGF2 knockout in myoblasts/myotubes, RNAPII ChIP-seq in KO cells Science advances Medium 31616795
2020 LEDGF/p75 differentially regulates HIV transcription: during latency it suppresses proviral transcription by recruiting PAF1 complex to promote RNAPII promoter-proximal pausing; upon latency reversal, casein kinase II (CKII)-dependent MLL1 complex competitively displaces PAF1 from LEDGF/p75 at the provirus, enabling Super Elongation Complex recruitment and transcriptional activation. Co-immunoprecipitation, ChIP for PAF1/MLL1/SEC at provirus, CKII pharmacological inhibition and depletion, HIV latency reversal assays Science advances High 32426500
2024 PSIP1 interacts with R-loops and proteins involved in R-loop homeostasis including PARP1; depletion of PSIP1 leads to genome-wide accumulation of R-loops and DNA damage (γ-H2AX) at gene promoters, local transcriptional arrest, transcription-replication conflicts, increased 53BP1 foci, and reduced RAD51 foci (indicating altered DNA repair pathway choice toward NHEJ); PSIP1 depletion sensitizes cancer cells to PARP1 inhibitors. Co-immunoprecipitation of PSIP1 with PARP1 and R-loop-associated proteins, genome-wide R-loop mapping (DRIP-seq), γ-H2AX ChIP-seq, 53BP1 and RAD51 foci analysis, cell viability assays with PARP inhibitors in PSIP1-depleted cells Nature communications High 38191578
2009 LEDGF/p75 binds the VEGF-C promoter (demonstrated by ChIP); FSH augments this binding and increases LEDGF/p75 mRNA and protein levels; siRNA suppression of LEDGF/p75 reduces hormonally induced VEGF-C expression, linking LEDGF/p75 to gonadotropin-regulated lymphangiogenesis in ovarian cancer cells. ChIP, siRNA knockdown, promoter-luciferase reporter assay, RT-PCR Cancer research Medium 19934313
2012 LEDGF/p75 and p52 both interact with MeCP2 in vitro and in human cancer cells; the interaction maps to the N-terminal PWWP-CR1 domain shared by both isoforms; LEDGF/p75 modulates MeCP2-induced Hsp27 promoter transactivation in a cell-context-dependent manner. Transcription factor protein arrays, pull-down, AlphaScreen, co-immunoprecipitation, nuclear co-localization by confocal microscopy, Hsp27 promoter reporter assays Molecular cancer research Medium 22275515
2003 LEDGF/p75 is cleaved by caspases at three sites during apoptosis, generating 65 kDa and 58 kDa fragments; caspase cleavage abolishes the survival function of LEDGF/p75. Immunoblotting of apoptotic cell extracts, caspase cleavage site mapping Autoimmunity reviews Medium 12965181
2004 LEDGF/p75 binds to and transactivates heat shock (nGAAn) and stress response elements (A/TGGGGA/T) in promoters of ADH1, ADH4, and RALDH2 genes; overexpression in lens epithelial cells elevates RA production and protects against ethanol stress. EMSA, supershift assay, CAT reporter transfection, RT-PCR in overexpressing cells American journal of physiology. Cell physiology Medium 15238362

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 HIV-1 integrase forms stable tetramers and associates with LEDGF/p75 protein in human cells. The Journal of biological chemistry 568 12407101
2003 LEDGF/p75 is essential for nuclear and chromosomal targeting of HIV-1 integrase in human cells. The Journal of biological chemistry 406 12796494
2007 LEDGF/p75 functions downstream from preintegration complex formation to effect gene-specific HIV-1 integration. Genes & development 390 17639082
2012 Psip1/Ledgf p52 binds methylated histone H3K36 and splicing factors and contributes to the regulation of alternative splicing. PLoS genetics 280 22615581
2007 Role of PSIP1/LEDGF/p75 in lentiviral infectivity and integration targeting. PloS one 201 18092005
2005 Integrase mutants defective for interaction with LEDGF/p75 are impaired in chromosome tethering and HIV-1 replication. The Journal of biological chemistry 197 15855167
2008 The lentiviral integrase binding protein LEDGF/p75 and HIV-1 replication. PLoS pathogens 187 18369482
2005 The interaction of LEDGF/p75 with integrase is lentivirus-specific and promotes DNA binding. The Journal of biological chemistry 173 15749713
2006 Transient and stable knockdown of the integrase cofactor LEDGF/p75 reveals its role in the replication cycle of human immunodeficiency virus. Journal of virology 171 16439544
2013 Structural basis for high-affinity binding of LEDGF PWWP to mononucleosomes. Nucleic acids research 162 23396443
2004 Anti-DFS70 antibodies in 597 healthy hospital workers. Arthritis and rheumatism 161 15022332
2012 LEDGF (p75) promotes DNA-end resection and homologous recombination. Nature structural & molecular biology 158 22773103
2006 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. Nucleic acids research 150 16549878
2006 LEDGF/p75 interacts with divergent lentiviral integrases and modulates their enzymatic activity in vitro. Nucleic acids research 147 17158150
2002 LEDGF, a survival factor, activates stress-related genes. Progress in retinal and eye research 134 12052388
2009 A novel co-crystal structure affords the design of gain-of-function lentiviral integrase mutants in the presence of modified PSIP1/LEDGF/p75. PLoS pathogens 133 19132083
2013 Nucleosomal DNA binding drives the recognition of H3K36-methylated nucleosomes by the PSIP1-PWWP domain. Epigenetics & chromatin 129 23656834
2010 LEDGF hybrids efficiently retarget lentiviral integration into heterochromatin. Molecular therapy : the journal of the American Society of Gene Therapy 126 20195265
2001 LEDGF binds to heat shock and stress-related element to activate the expression of stress-related genes. Biochemical and biophysical research communications 117 11350077
2008 Dynamic modulation of HIV-1 integrase structure and function by cellular lens epithelium-derived growth factor (LEDGF) protein. The Journal of biological chemistry 115 18801737
2008 Integrase, LEDGF/p75 and HIV replication. Cellular and molecular life sciences : CMLS 112 18264802
2006 Identification of the LEDGF/p75 binding site in HIV-1 integrase. Journal of molecular biology 108 17137594
2005 Antinuclear autoantibodies in prostate cancer: immunity to LEDGF/p75, a survival protein highly expressed in prostate tumors and cleaved during apoptosis. The Prostate 108 15389814
2012 Differential effects of human immunodeficiency virus type 1 capsid and cellular factors nucleoporin 153 and LEDGF/p75 on the efficiency and specificity of viral DNA integration. Journal of virology 103 23097450
2009 Docetaxel-induced prostate cancer cell death involves concomitant activation of caspase and lysosomal pathways and is attenuated by LEDGF/p75. Molecular cancer 100 19715609
2013 The LEDGF/p75 integrase interaction, a novel target for anti-HIV therapy. Virology 96 23217620
2007 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. PLoS pathogens 91 17397262
2000 Lens epithelium-derived growth factor (LEDGF/p75) and p52 are derived from a single gene by alternative splicing. Gene 88 10721720
2015 LEDGF/p75 interacts with mRNA splicing factors and targets HIV-1 integration to highly spliced genes. Genes & development 87 26545813
2006 Retroviral DNA integration: HIV and the role of LEDGF/p75. Trends in genetics : TIG 87 16730094
2006 Disruption of Ledgf/Psip1 results in perinatal mortality and homeotic skeletal transformations. Molecular and cellular biology 86 16980622
2005 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 86 16337983
2004 Identification and characterization of a functional nuclear localization signal in the HIV-1 integrase interactor LEDGF/p75. The Journal of biological chemistry 85 15163664
2012 HRP2 determines the efficiency and specificity of HIV-1 integration in LEDGF/p75 knockout cells but does not contribute to the antiviral activity of a potent LEDGF/p75-binding site integrase inhibitor. Nucleic acids research 82 23042676
2019 LEDGF and HDGF2 relieve the nucleosome-induced barrier to transcription in differentiated cells. Science advances 76 31616795
2008 High concomitance of disease marker autoantibodies in anti-DFS70/LEDGF autoantibody-positive patients with autoimmune rheumatic disease. Lupus 74 18372356
2015 The significance of autoantibodies to DFS70/LEDGFp75 in health and disease: integrating basic science with clinical understanding. Clinical and experimental medicine 70 26088181
2007 Differential interaction of HIV-1 integrase and JPO2 with the C terminus of LEDGF/p75. Journal of molecular biology 68 17669426
2001 Spatial and temporal dynamics of two alternatively spliced regulatory factors, lens epithelium-derived growth factor (ledgf/p75) and p52, in the nucleus. Cell and tissue research 67 11512661
2014 TALEN knockout of the PSIP1 gene in human cells: analyses of HIV-1 replication and allosteric integrase inhibitor mechanism. Journal of virology 63 24942577
2003 LEDGF/p75: a novel nuclear autoantigen at the crossroads of cell survival and apoptosis. Autoimmunity reviews 63 12965181
2010 High-resolution profiling of the LEDGF/p75 chromatin interaction in the ENCODE region. Nucleic acids research 62 20484370
2008 Identification and characterization of PWWP domain residues critical for LEDGF/p75 chromatin binding and human immunodeficiency virus type 1 infectivity. Journal of virology 60 18799576
2000 Activation of LEDGF gene by thermal-and oxidative-stresses. Biochemical and biophysical research communications 60 11027629
2012 HRP-2 determines HIV-1 integration site selection in LEDGF/p75 depleted cells. Retrovirology 58 23046603
2005 DNA binding domains and nuclear localization signal of LEDGF: contribution of two helix-turn-helix (HTH)-like domains and a stretch of 58 amino acids of the N-terminal to the trans-activation potential of LEDGF. Journal of molecular biology 58 16318853
2009 Transcriptional co-activator LEDGF interacts with Cdc7-activator of S-phase kinase (ASK) and stimulates its enzymatic activity. The Journal of biological chemistry 56 19864417
2007 LEDGF/p75 has increased expression in blasts from chemotherapy-resistant human acute myelogenic leukemia patients and protects leukemia cells from apoptosis in vitro. Molecular cancer 56 17451600
2017 LEDGF/p75 is dispensable for hematopoiesis but essential for MLL-rearranged leukemogenesis. Blood 53 29084774
2000 LEDGF: survival of embryonic chick retinal photoreceptor cells. Investigative ophthalmology & visual science 53 10752956
2010 The transcriptional co-activator LEDGF/p75 displays a dynamic scan-and-lock mechanism for chromatin tethering. Nucleic acids research 52 20974633
2012 Expression of the stress response oncoprotein LEDGF/p75 in human cancer: a study of 21 tumor types. PloS one 51 22276150
2008 Chromatinized templates reveal the requirement for the LEDGF/p75 PWWP domain during HIV-1 integration in vitro. Nucleic acids research 50 18174227
2004 Autoantibodies to DFS70/LEDGF are increased in alopecia areata patients. Journal of autoimmunity 48 15501396
2011 FRET analysis reveals distinct conformations of IN tetramers in the presence of viral DNA or LEDGF/p75. Nucleic acids research 47 21771857
2007 Transcriptional coactivator LEDGF/p75 modulates human immunodeficiency virus type 1 integrase-mediated concerted integration. Journal of virology 47 17267486
2014 Validation and structural characterization of the LEDGF/p75-MLL interface as a new target for the treatment of MLL-dependent leukemia. Cancer research 46 25082813
2012 The stress oncoprotein LEDGF/p75 interacts with the methyl CpG binding protein MeCP2 and influences its transcriptional activity. Molecular cancer research : MCR 46 22275515
2009 Gonadotropin-regulated lymphangiogenesis in ovarian cancer is mediated by LEDGF-induced expression of VEGF-C. Cancer research 46 19934313
2013 Impairing MLL-fusion gene-mediated transformation by dissecting critical interactions with the lens epithelium-derived growth factor (LEDGF/p75). Leukemia 44 23318960
2000 Review: Age-related cataract: immunity and lens epithelium-derived growth factor (LEDGF). Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics 44 10803429
2007 Antibodies to the lens and cornea in anti-DFS70-positive subjects. Annals of the New York Academy of Sciences 40 17804545
2001 Fusion of the NUP98 gene with the LEDGF/p52 gene defines a recurrent acute myeloid leukemia translocation. BMC genetics 38 11737860
2020 Twenty years of research on the DFS70/LEDGF autoantibody-autoantigen system: many lessons learned but still many questions. Auto- immunity highlights 37 32127038
2015 DFS70/LEDGFp75: An Enigmatic Autoantigen at the Interface between Autoimmunity, AIDS, and Cancer. Frontiers in immunology 37 25852687
2014 Oncogenic human papillomaviruses activate the tumor-associated lens epithelial-derived growth factor (LEDGF) gene. PLoS pathogens 36 24604027
2008 Alternative splicing and caspase-mediated cleavage generate antagonistic variants of the stress oncoprotein LEDGF/p75. Molecular cancer research : MCR 35 18708362
2017 PSIP1/p75 promotes tumorigenicity in breast cancer cells by promoting the transcription of cell cycle genes. Carcinogenesis 34 28633434
2016 LEDGF/p75 Overexpression Attenuates Oxidative Stress-Induced Necrosis and Upregulates the Oxidoreductase ERP57/PDIA3/GRP58 in Prostate Cancer. PloS one 33 26771192
2000 Heparin's roles in stabilizing, potentiating, and transporting LEDGF into the nucleus. Investigative ophthalmology & visual science 33 10937578
2021 A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. PLoS pathogens 32 34293041
2016 Autoantibodies Against DFS70/LEDGF Exclusion Markers for Systemic Autoimmune Rheumatic Diseases (SARD). Clinical laboratory 32 27215068
2012 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 & disease 32 22647853
2011 Nuclear protein LEDGF/p75 recognizes supercoiled DNA by a novel DNA-binding domain. Nucleic acids research 32 21345933
2011 Inhibitors of the interactions between HIV-1 IN and the cofactor LEDGF/p75. ChemMedChem 31 21506277
2011 LEDGF dominant interference proteins demonstrate prenuclear exposure of HIV-1 integrase and synergize with LEDGF depletion to destroy viral infectivity. Journal of virology 30 21270171
2016 Anti-DFS70 antibodies detected by immunoblot methods: A reliable tool to confirm the dense fine speckles ANA pattern. Journal of immunological methods 29 27374867
2015 Specificity of antinuclear autoantibodies recognizing the dense fine speckled nuclear pattern: Preferential targeting of DFS70/LEDGFp75 over its interacting partner MeCP2. Clinical immunology (Orlando, Fla.) 29 26235378
2013 Structural and functional role of INI1 and LEDGF in the HIV-1 preintegration complex. PloS one 29 23593299
2012 Expression analysis of LEDGF/p75, APOBEC3G, TRIM5alpha, and tetherin in a Senegalese cohort of HIV-1-exposed seronegative individuals. PloS one 29 22479480
2012 Transcriptional protein Sp1 regulates LEDGF transcription by directly interacting with its cis-elements in GC-rich region of TATA-less gene promoter. PloS one 29 22615874
2006 LEDGF/DFS70, a major autoantigen of atopic dermatitis, is a component of keratohyalin granules. The Journal of investigative dermatology 29 16858421
2004 Lens epithelium-derived growth factor (LEDGF/p75) expression in fetal and adult human brain. Experimental eye research 29 15642333
2011 IgE and IgG(4) autoantibodies against DFS70/LEDGF in atopic dermatitis. Autoimmunity 28 21329475
2009 Virological and cellular roles of the transcriptional coactivator LEDGF/p75. Current topics in microbiology and immunology 28 20012527
2011 In vitro DNA tethering of HIV-1 integrase by the transcriptional coactivator LEDGF/p75. Journal of molecular biology 27 21763490
2017 Protein-protein and protein-chromatin interactions of LEDGF/p75 as novel drug targets. Drug discovery today. Technologies 26 29233296
2014 Blocking the interaction between HIV-1 integrase and human LEDGF/p75: mutational studies, virtual screening and molecular dynamics simulations. Molecular bioSystems 26 24389668
2010 Overexpression of LEDGF/DFS70 induces IL-6 via p38 activation in HaCaT cells, similar to that seen in the psoriatic condition. The Journal of investigative dermatology 26 20631726
2009 Integration of HIV-1 DNA is regulated by interplay between viral rev and cellular LEDGF/p75 proteins. Molecular medicine (Cambridge, Mass.) 26 19855849
2020 Competition between PAF1 and MLL1/COMPASS confers the opposing function of LEDGF/p75 in HIV latency and proviral reactivation. Science advances 24 32426500
2017 Targeting the stress oncoprotein LEDGF/p75 to sensitize chemoresistant prostate cancer cells to taxanes. Oncotarget 24 28212536
2017 Psip1/p52 regulates posterior Hoxa genes through activation of lncRNA Hottip. PLoS genetics 24 28384324
2004 LEDGF regulation of alcohol and aldehyde dehydrogenases in lens epithelial cells: stimulation of retinoic acid production and protection from ethanol toxicity. American journal of physiology. Cell physiology 24 15238362
2003 LEDGF activation of PKC gamma and gap junction disassembly in lens epithelial cells. Experimental eye research 24 12697420
2017 Analysis of DFS70 pattern and impact on ANA screening using a novel HEp-2 ELITE/DFS70 knockout substrate. Auto- immunity highlights 23 28315185
2017 The HIV-1 integrase-LEDGF allosteric inhibitor MUT-A: resistance profile, impairment of virus maturation and infectivity but without influence on RNA packaging or virus immunoreactivity. Retrovirology 23 29121950
2014 Structure, mechanics, and binding mode heterogeneity of LEDGF/p75-DNA nucleoprotein complexes revealed by scanning force microscopy. Nanoscale 23 24632996
2012 Discovery of novel inhibitors of LEDGF/p75-IN protein-protein interactions. Bioorganic & medicinal chemistry 23 23306052
2024 PSIP1/LEDGF reduces R-loops at transcription sites to maintain genome integrity. Nature communications 22 38191578

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