ArticleThe Journal of biological chemistry2010
Transcriptional co-activator LEDGF interacts with Cdc7-activator of S-phase kinase (ASK) and stimulates its enzymatic activity.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 66 citations in OpenAlex.
- Structural mechanism for the selective phosphorylation of DNA-loaded MCM double hexamers by the Dbf4-dependent kinase.Nature structural & molecular biology · 2022Article
- Article
- Article
- Structural Basis for the Activation and Target Site Specificity of CDC7 Kinase.Structure (London, England : 1993) · 2020Article
- Article
- Targeted editing of the PSIP1 gene encoding LEDGF/p75 protects cells against HIV infection.Scientific reports · 2019Article
- TheJournal of cell science · 2019Article
- Affinity switching of the LEDGF/p75 IBD interactome is governed by kinase-dependent phosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Interactions between Retroviruses and the Host Cell Genome.Molecular therapy. Methods & clinical development · 2018Review
- Recognition and Relevance of Anti-DFS70 Autoantibodies in Routine Antinuclear Autoantibodies Testing at a Community Hospital.Frontiers in medicine · 2018Article
- PSIP1/p75 promotes tumorigenicity in breast cancer cells by promoting the transcription of cell cycle genes.Carcinogenesis · 2017Article
- H3K36me3 and PSIP1/LEDGF associate with several DNA repair proteins, suggesting their role in efficient DNA repair at actively transcribing loci.Wellcome open research · 2017Article
- Retroviral DNA Integration.Chemical reviews · 2016Review
- The significance of autoantibodies to DFS70/LEDGFp75 in health and disease: integrating basic science with clinical understanding.Clinical and experimental medicine · 2016Review
- Towards a Safer, More Randomized Lentiviral Vector Integration Profile Exploring Artificial LEDGF Chimeras.PloS one · 2016Article
- 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.) · 2015Article
- Multiple cellular proteins interact with LEDGF/p75 through a conserved unstructured consensus motif.Nature communications · 2015Article
- Characterization of a Drosophila ortholog of the Cdc7 kinase: a role for Cdc7 in endoreplication independent of Chiffon.The Journal of biological chemistry · 2015Article
- Embryonic Lethality Due to Arrested Cardiac Development in Psip1/Hdgfrp2 Double-Deficient Mice.PloS one · 2015Article
- Dynamics of the ternary complex formed by c-Myc interactor JPO2, transcriptional co-activator LEDGF/p75, and chromatin.The Journal of biological chemistry · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Lens epithelium-derived growth factor (LEDGF) is an important co-factor of human immunodeficiency virus DNA integration; however, its cellular functions are poorly characterized. We now report identification of the Cdc7-activator of S-phase kinase (ASK) heterodimer as a novel interactor of LEDGF. Both kinase subunits co-immunoprecipitated with endogenous LEDGF from human cell extracts. Truncation analyses identified the integrase-binding domain of LEDGF as essential and minimally sufficient for the interaction with Cdc7-ASK. Reciprocally, the interaction required autophosphorylation of the kinase and the presence of 50 C-terminal residues of ASK. The kinase phosphorylated LEDGF in vitro, with Ser-206 being the major target, and LEDGF phosphorylated at this residue could be detected during S phase of the cell cycle. LEDGF potently stimulated the enzymatic activity of Cdc7-ASK, increasing phosphorylation of MCM2 in vitro by more than 10-fold. This enzymatic stimulation as well as phosphorylation of LEDGF depended on the protein-protein interaction. Intriguingly, removing the C-terminal region of ASK, involved in the interaction with LEDGF, resulted in a hyperactive kinase. Our results indicate that the interaction with LEDGF relieves autoinhibition of Cdc7-ASK kinase, imposed by the C terminus of ASK.
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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.