ArticleGenes & development2017
The SIAH E3 ubiquitin ligases promote Wnt/β-catenin signaling through mediating Wnt-induced Axin degradation.
Article in Genes & development, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 103 citations in OpenAlex.
- The autoimmune regulator (AIRE) is a target of the E3-Ubiquitin ligase Seven-in-absentia homolog 1 (SIAH1).Apoptosis : an international journal on programmed cell death · 2026Article
- An SLCO2B1 mRNA Isoform Acts as a Noncoding RNA to Drive Cancer Progression by Triggering Protein Biosynthesis.Cancer research · 2026Article
- Ras-MAPK inhibition induces AXIN1 loss in colorectal cancer by mTOR associated suppression of protein synthesis.Cell communication and signaling : CCS · 2026Article
- Phenylethanoid Glycosides fromInternational journal of molecular sciences · 2026Article
- Hepatocellular carcinoma-linkediScience · 2026Article
- Dorsal determinant Hwa stabilizes β-catenin through direct inhibition of GSK3.Genes & development · 2026Article
- Targeting TRIM15-mediated Axin1 depolymerization suppresses Wnt signaling and inhibits colorectal cancer growth.Cell death & disease · 2025Article
- Wnt signalosome assembly is governed by conformational flexibility of Axin and by the AP2 clathrin adaptor.Nature communications · 2025Article
- NovelCase reports in genetics · 2025Article
- A novel variant inFrontiers in neuroscience · 2025Article
- The CK1ε/SIAH1 axis regulates AXIN1 stability in colorectal cancer cells.Molecular oncology · 2024Article
- The Role of Ubiquitination in Osteosarcoma Development and Therapies.Biomolecules · 2024Review
- Analysis of Tumor-Associated AXIN1 Missense Mutations Identifies Variants That Activate β-Catenin Signaling.Cancer research · 2024Article
- New insights in ubiquitin-dependent Wnt receptor regulation in tumorigenesis.In vitro cellular & developmental biology. Animal · 2024Review
- The cross talk of ubiquitination and chemotherapy tolerance in colorectal cancer.Journal of cancer research and clinical oncology · 2024Review
- BIRC6 Modulates the Protein Stability of Axin to Regulate the Growth, Stemness, and Resistance of Renal Cancer Cells via the β-Catenin Pathway.ACS omega · 2024Article
- The important regulatory roles of circRNA‑encoded proteins or peptides in cancer pathogenesis (Review).International journal of oncology · 2024Review
- The scaffold protein AXIN1: gene ontology, signal network, and physiological function.Cell communication and signaling : CCS · 2024Review
- R-spondin-1 induces Axin degradation via the LRP6-CK1ε axis.Cell communication and signaling : CCS · 2024Article
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Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Wnt/β-catenin signaling pathway plays essential roles in embryonic development and adult tissue homeostasis. Axin is a concentration-limiting factor responsible for the formation of the β-catenin destruction complex. Wnt signaling itself promotes the degradation of Axin. However, the underlying molecular mechanism and biological relevance of this targeting of Axin have not been elucidated. Here, we identify SIAH1/2 (SIAH) as the E3 ligase mediating Wnt-induced Axin degradation. SIAH proteins promote the ubiquitination and proteasomal degradation of Axin through interacting with a VxP motif in the GSK3-binding domain of Axin, and this function of SIAH is counteracted by GSK3 binding to Axin. Structural analysis reveals that the Axin segment responsible for SIAH binding is also involved in GSK3 binding but adopts distinct conformations in Axin/SIAH and Axin/GSK3 complexes. Knockout of SIAH1 blocks Wnt-induced Axin ubiquitination and attenuates Wnt-induced β-catenin stabilization. Our data suggest that Wnt-induced dissociation of the Axin/GSK3 complex allows SIAH to interact with Axin not associated with GSK3 and promote its degradation and that SIAH-mediated Axin degradation represents an important feed-forward mechanism to achieve sustained Wnt/β-catenin signaling.
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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.