ArticleMolecular and cellular biology2018
Regulation of Transcription Factor SP1 by the β-Catenin Destruction Complex Modulates Wnt Response.
Article in Molecular and cellular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- SP1 Expression and the Clinicopathological Features of Tumors: A Meta-Analysis and Bioinformatics Analysis.Pathology oncology research : POR · 2021Pooled it
- Orexin B Reduces Cerebral Aneurysms Through Inhibition of SP-1.CNS neuroscience & therapeutics · 2026Article
- Unraveling the role of specificity protein 1 in gliomas: pathophysiology and clinical implications.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Pan-cancer drivers of metastasis.Molecular cancer · 2025Article
- The Loss of an Orphan Nuclear Receptor NR2E3 Augments Wnt/β-catenin Signaling via Epigenetic Dysregulation that Enhances Sp1-β catenin-p300 Interactions in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- SETDB1 as a cancer target: challenges and perspectives in drug design.RSC medicinal chemistry · 2024Review
- Androgen deprivation induces double-null prostate cancer via aberrant nuclear export and ribosomal biogenesis through HGF and Wnt activation.Nature communications · 2024Article
- The scaffold protein AXIN1: gene ontology, signal network, and physiological function.Cell communication and signaling : CCS · 2024Review
- PGF2alpha Inhibits 20alpha-HSD Expression by Suppressing CK1alpha-induced ERK and SP1 Activation in the Corpus Luteum of Pregnant Mice.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
- Host-gut microbiota derived secondary metabolite mediated regulation of Wnt/β-catenin pathway: a potential therapeutic axis in IBD and CRC.Frontiers in oncology · 2024Review
- Role of post-translational modifications of Sp1 in cancer: state of the art.Frontiers in cell and developmental biology · 2024Review
- Inhibition of USP7 upregulates USP22 and activates its downstream cancer-related signaling pathways in human cancer cells.Cell communication and signaling : CCS · 2023Article
- LncRNA SNHG4 Modulates EMT Signal and Antitumor Effects in Endometrial Cancer through Transcription Factor SP-1.Biomedicines · 2023Article
- Sp1-Induced SETDB1 Overexpression Transcriptionally Inhibits HPGD in a β-Catenin-Dependent Manner and Promotes the Proliferation and Metastasis of Gastric Cancer.Journal of gastric cancer · 2022Article
- Review
- Hsa_circ_0026628 promotes the development of colorectal cancer by targeting SP1 to activate the Wnt/β-catenin pathway.Cell death & disease · 2021Article
- Identification of response signatures for tankyrase inhibitor treatment in tumor cell lines.iScience · 2021Article
- Article
- Epigenetic Regulation of the Wnt/β-Catenin Signaling Pathway in Cancer.Frontiers in genetics · 2021Review
- Hormone-Responsive BMP Signaling Expands Myoepithelial Cell Lineages and Prevents Alveolar Precocity in Mammary Gland.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ubiquitous transcription factor specificity protein 1 (SP1) is heavily modified posttranslationally. These modifications are critical for switching its functions and modulation of its transcriptional activity and DNA binding and stability. However, the mechanism governing the stability of SP1 by cellular signaling pathways is not well understood. Here, we provide biochemical and functional evidence that SP1 is an integral part of the Wnt signaling pathway. We identified a phosphodegron motif in SP1 that is specific to mammals. In the absence of Wnt signaling, glycogen synthase kinase 3β (GSK3β)-mediated phosphorylation and β-TrCP E3 ubiquitin ligase-mediated ubiquitination are required to induce SP1 degradation. When Wnt signaling is on, SP1 is stabilized in a β-catenin-dependent manner. SP1 directly interacts with β-catenin, and Wnt signaling induces the stabilization of SP1 by impeding its interaction with β-TrCP and axin1, components of the destruction complex. Wnt signaling suppresses ubiquitination and subsequent proteosomal degradation of SP1. Furthermore, SP1 regulates Wnt-dependent stability of β-catenin and their mutual stabilization is critical for target gene expression, suggesting a feedback mechanism. Upon stabilization, SP1 and β-catenin cooccupy the promoters of TCFL2/β-catenin target genes. Collectively, this study uncovers a direct link between SP1 and β-catenin in the Wnt signaling pathway.
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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.