ArticleProceedings of the National Academy of Sciences of the United States of America2018
Affinity switching of the LEDGF/p75 IBD interactome is governed by kinase-dependent phosphorylation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- Structure and function of IWS1 in transcription elongation.Nucleic acids research · 2026Article
- Sequence-Dependent Heterotypic Assemblies of Intrinsically Disordered Peptides.ChemistryEurope · 2026Article
- Absence of Ledgf in mouse brain affects the Kmt2a/b and polycomb balance, synaptic transmission and motor function.Acta neuropathologica communications · 2026Article
- Co-targeting menin and LSD1 dismantles oncogenic programs and restores differentiation in MLL-rearranged AML.bioRxiv : the preprint server for biology · 2025Article
- Inherent asymmetry of Rpd3S coordinates its nucleosome engagement and association with elongating RNA polymerase II.Nature structural & molecular biology · 2025Article
- LEDGF/p75 promotes transcriptional pausing through preventing SPT5 phosphorylation.Science advances · 2025Article
- Review
- The Impact of Lens Epithelium-Derived Growth Factor p75 Dimerization on Its Tethering Function.Cells · 2024Article
- Multivalency of nucleosome recognition by LEDGF.Nucleic acids research · 2023Article
- Interaction modules that impart specificity to disordered protein.Trends in biochemical sciences · 2023Review
- The TFIIS N-terminal domain (TND): a transcription assembly module at the interface of order and disorder.Biochemical Society transactions · 2023Review
- Identification of the H3K36me3 reader LEDGF/p75 in the pancancer landscape and functional exploration in clear cell renal cell carcinoma.Computational and structural biotechnology journal · 2023Article
- The phosphorylation to acetylation/methylation cascade in transcriptional regulation: how kinases regulate transcriptional activities of DNA/histone-modifying enzymes.Cell & bioscience · 2022Review
- The MYC oncoprotein directly interacts with its chromatin cofactor PNUTS to recruit PP1 phosphatase.Nucleic acids research · 2022Article
- LEDGF/p75-mediated chemoresistance of mixed-lineage leukemia involves cell survival pathways and super enhancer activators.Cancer gene therapy · 2022Review
- Pharmacological perspectives and molecular mechanisms of coumarin derivatives against virus disease.Genes & diseases · 2022Review
- A ubiquitous disordered protein interaction module orchestrates transcription elongation.Science (New York, N.Y.) · 2021Article
- Article
- Structure, function and inhibition of critical protein-protein interactions involving mixed lineage leukemia 1 and its fusion oncoproteins.Journal of hematology & oncology · 2021Review
- Article
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 3 countries.
Funding
Abstract
Lens epithelium-derived growth factor/p75 (LEDGF/p75, or PSIP1) is a transcriptional coactivator that tethers other proteins to gene bodies. The chromatin tethering function of LEDGF/p75 is hijacked by HIV integrase to ensure viral integration at sites of active transcription. LEDGF/p75 is also important for the development of mixed-lineage leukemia (MLL), where it tethers the MLL1 fusion complex at aberrant MLL targets, inducing malignant transformation. However, little is known about how the LEDGF/p75 protein interaction network is regulated. Here, we obtained solution structures of the complete interfaces between the LEDGF/p75 integrase binding domain (IBD) and its cellular binding partners and validated another binding partner, Mediator subunit 1 (MED1). We reveal that structurally conserved IBD-binding motifs (IBMs) on known LEDGF/p75 binding partners can be regulated by phosphorylation, permitting switching between low- and high-affinity states. Finally, we show that elimination of IBM phosphorylation sites on MLL1 disrupts the oncogenic potential of primary MLL1-rearranged leukemic cells. Our results demonstrate that kinase-dependent phosphorylation of MLL1 represents a previously unknown oncogenic dependency that may be harnessed in the treatment of MLL-rearranged leukemia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.