ArticleScientific reports2017
FKBP65-dependent peptidyl-prolyl isomerase activity potentiates the lysyl hydroxylase 2-driven collagen cross-link switch.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Exploring mechanisms of scar-free skin wound healing in adult zebrafish in comparison to mouse.PLoS genetics · 2026Article
- Clinical Variability Within theGenes · 2026Article
- FKBP10 expression and TP53 mutation predict prognosis and chemotherapy response in triple-negative breast cancer.Discover oncology · 2025Article
- Generation of bone-specific lysyl hydroxylase 2 knockout mice and their phenotypes.Biochemistry and biophysics reports · 2024Article
- A novel compound heterozygous variation in theHeliyon · 2024Article
- Computational identification and experimental verification of a novel signature based on SARS-CoV-2-related genes for predicting prognosis, immune microenvironment and therapeutic strategies in lung adenocarcinoma patients.Frontiers in immunology · 2024Article
- Comparative mucomic analysis of three functionally distinct Cornu aspersum Secretions.Nature communications · 2023Article
- Melanoma-intrinsic NR2F6 activity regulates antitumor immunity.Science advances · 2023Article
- Genetic Analysis and Functional Study of a Pedigree With Bruck Syndrome Caused byFrontiers in pediatrics · 2022Article
- Case Report: Exome Sequencing Identified a Novel Compound Heterozygous Variation inFrontiers in genetics · 2021Article
- PLOD2 Is Essential to Functional Activation of Integrin β1 for Invasion/Metastasis in Head and Neck Squamous Cell Carcinomas.iScience · 2020Article
- FKBP10 Acts as a New Biomarker for Prognosis and Lymph Node Metastasis of Gastric Cancer by Bioinformatics Analysis and in Vitro Experiments.OncoTargets and therapy · 2020Article
- Lysyl hydroxylase 3 increases collagen deposition and promotes pulmonary fibrosis by activating TGFβ1/Smad3 and Wnt/β-catenin pathways.Archives of medical science : AMS · 2020Article
- Comprehensive evaluation of FKBP10 expression and its prognostic potential in gastric cancer.Oncology reports · 2019Article
- Cyclophilin B control of lysine post-translational modifications of skin type I collagen.PLoS genetics · 2019Article
- The fibrotic tumor stroma.The Journal of clinical investigation · 2018Review
- FKBP Ligands-Where We Are and Where to Go?Frontiers in pharmacology · 2018Review
- Heat shock protein 47 and 65-kDa FK506-binding protein weakly but synergistically interact during collagen folding in the endoplasmic reticulum.The Journal of biological chemistry · 2017Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Bruck Syndrome is a connective tissue disease associated with inactivating mutations in lysyl hydroxylase 2 (LH2/PLOD2) or FK506 binding protein 65 (FKBP65/FKBP10). However, the functional relationship between LH2 and FKBP65 remains unclear. Here, we postulated that peptidyl prolyl isomerase (PPIase) activity of FKBP65 positively modulates LH2 enzymatic activity and is critical for the formation of hydroxylysine-aldehyde derived intermolecular collagen cross-links (HLCCs). To test this hypothesis, we analyzed collagen cross-links in Fkbp10-null and -wild-type murine embryonic fibroblasts. Although LH2 protein levels did not change, FKBP65 deficiency significantly diminished HLCCs and increased the non-hydroxylated lysine-aldehyde-derived collagen cross-links (LCCs), a pattern consistent with loss of LH2 enzymatic activity. The HLCC-to-LCC ratio was rescued in FKBP65-deficient murine embryonic fibroblasts by reconstitution with wild-type but not mutant FKBP65 that lacks intact PPIase domains. Findings from co-immunoprecipitation, protein-fragment complementation, and co-immunofluorescence assays showed that LH2 and FKBP65 are part of a common protein complex. We conclude that FKBP65 regulates LH2-mediated collagen cross-linking. Because LH2 promotes fibrosis and cancer metastasis, our findings suggest that pharmacologic strategies to target FKBP65 and LH2 may have complementary therapeutic activities.
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