ArticleThe Journal of biological chemistry2016
Characterization of Tiki, a New Family of Wnt-specific Metalloproteases.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
29 citing papers in PubMed.
- Article
- Tiki2 restrains Wnt5a/Ror signaling to limit inflammation in acute kidney injury.Communications biology · 2026Article
- Secreted frizzled-related proteins in angiogenesis: molecular mechanisms and clinical implications.Angiogenesis · 2025Review
- Wnt/β-catenin signaling pathway in carcinogenesis and cancer therapy.Journal of hematology & oncology · 2024Review
- Article
- The WNT/β-catenin system in chronic kidney disease-mineral bone disorder syndrome.International urology and nephrology · 2023Review
- Frizzled receptors facilitate Tiki inhibition of Wnt signaling at the cell surface.EMBO reports · 2023Article
- Structure of the Wnt-Frizzled-LRP6 initiation complex reveals the basis for coreceptor discrimination.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- First Characterization of the Transcriptome of Lung Fibroblasts of SSc Patients and Healthy Donors of African Ancestry.International journal of molecular sciences · 2023Article
- Therapeutic approaches to activate the canonical Wnt pathway for bone regeneration.Journal of tissue engineering and regenerative medicine · 2022Review
- Tiki proteins are glycosylphosphatidylinositol-anchored proteases.FEBS letters · 2022Article
- The role of Wnt/mTOR signaling in spinal cord injury.Journal of clinical orthopaedics and trauma · 2022Review
- Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities.Signal transduction and targeted therapy · 2022Review
- Misregulation of Wnt Signaling Pathways at the Plasma Membrane in Brain and Metabolic Diseases.Membranes · 2021Review
- Wg secreted by conventional Golgi transport diffuses and forms Wg gradient whereas Wg tethered to extracellular vesicles do not diffuse.Cell death and differentiation · 2021Article
- Targeting Wnt Signaling for Gastrointestinal Cancer Therapy: Present and Evolving Views.Cancers · 2020Review
- Membrane metalloprotease TRABD2A restricts HIV-1 progeny production in resting CD4Nature immunology · 2019Article
- NOTUM inhibition increases endocortical bone formation and bone strength.Bone research · 2019Article
- Structural basis of inactivation of Ras and Rap1 small GTPases by Ras/Rap1-specific endopeptidase from the sepsis-causing pathogenThe Journal of biological chemistry · 2018Article
- The bacterial Ras/Rap1 site-specific endopeptidase RRSP cleaves Ras through an atypical mechanism to disrupt Ras-ERK signaling.Science signaling · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors.
Funding
Abstract
The Wnt family of secreted glycolipoproteins plays pivotal roles in development and human diseases. Tiki family proteins were identified as novel Wnt inhibitors that act by cleaving the Wnt amino-terminal region to inactivate specific Wnt ligands. Tiki represents a new metalloprotease family that is dependent on Mn(2+)/Co(2+) but lacks known metalloprotease motifs. The Tiki extracellular domain shares homology with bacterial TraB/PrgY proteins, known for their roles in the inhibition of mating pheromones. The TIKI/TraB fold is predicted to be distantly related to structures of additional bacterial proteins and may use a core β-sheet within an α+β-fold to coordinate conserved residues for catalysis. In this study, using assays for Wnt3a cleavage and signaling inhibition, we performed mutagenesis analyses of human TIKI2 to examine the structural prediction and identify the active site residues. We also established an in vitro assay for TIKI2 protease activity using FRET peptide substrates derived from the cleavage motifs of Wnt3a and Xenopus wnt8 (Xwnt8). We further identified two pairs of potential disulfide bonds that reside outside the β-sheet catalytic core but likely assist the folding of the TIKI domain. Finally, we systematically analyzed TIKI2 cleavage of the 19 human WNT proteins, of which we identified 10 as potential TIKI2 substrates, revealing the hydrophobic nature of Tiki cleavage sites. Our study provides insights into the Tiki family of proteases and its Wnt substrates.
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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.