ArticleJournal of molecular biology2012
Biophysical basis of the binding of WWOX tumor suppressor to WBP1 and WBP2 adaptors.
Article in Journal of molecular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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.
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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
31 citing papers in PubMed, 38 citations in OpenAlex.
- Identification and validation of an interaction between the E3 ubiquitin ligase WWP1 and the Transcriptional Co-Activator WBP2 in the human heart.Biology open · 2026Article
- The generation of stable microvessels in ischemia is mediated by endothelial cell derived TRAIL.Science advances · 2024Article
- Intramolecular autoinhibition regulates the selectivity of PRPF40A tandem WW domains for proline-rich motifs.Nature communications · 2024Article
- WW domain binding protein 2 (WBP2) as an oncogene in breast cancer: mechanisms and therapeutic prospects-a narrative review.Gland surgery · 2022Review
- Mechanosensitive Steroid Hormone Signaling and Cell Fate.Endocrinology · 2022Article
- Review
- The emerging roles of WBP2 oncogene in human cancers.Oncogene · 2020Review
- Decoding the link between WWOX and p53 in aggressive breast cancer.Cell cycle (Georgetown, Tex.) · 2019Review
- Interaction of WBP2 with ERα increases doxorubicin resistance of breast cancer cells by modulating MDR1 transcription.British journal of cancer · 2018Article
- Cancerous Protein Network That Inhibits the Tumor Suppressor Function of WW Domain-Containing Oxidoreductase (WWOX) by Aberrantly Expressed Molecules.Frontiers in oncology · 2018Review
- WW-Domain Containing Protein Roles in Breast Tumorigenesis.Frontiers in oncology · 2018Review
- Delineating WWOX Protein Interactome by Tandem Affinity Purification-Mass Spectrometry: Identification of Top Interactors and Key Metabolic Pathways Involved.Frontiers in oncology · 2018Article
- WWOX Phosphorylation, Signaling, and Role in Neurodegeneration.Frontiers in neuroscience · 2018Review
- Review
- WW domain-binding protein 2: an adaptor protein closely linked to the development of breast cancer.Molecular cancer · 2017Review
- FlexPepDock lessons from CAPRI peptide-protein rounds and suggested new criteria for assessment of model quality and utility.Proteins · 2017Article
- Pleiotropic Functions of Tumor Suppressor WWOX in Normal and Cancer Cells.The Journal of biological chemistry · 2015Review
- Allostery mediates ligand binding to WWOX tumor suppressor via a conformational switch.Journal of molecular recognition : JMR · 2015Article
- Structural insights into the functional versatility of WW domain-containing oxidoreductase tumor suppressor.Experimental biology and medicine (Maywood, N.J.) · 2015Review
- Role of WW domain proteins WWOX in development, prognosis, and treatment response of glioma.Experimental biology and medicine (Maywood, N.J.) · 2015Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
The WW-containing oxidoreductase (WWOX) tumor suppressor participates in a diverse array of cellular activities by virtue of its ability to recognize WW-binding protein 1 (WBP1) and WW-binding protein 2 (WBP2) signaling adaptors among a wide variety of other ligands. Herein, using a multitude of biophysical techniques, we provide evidence that while the WW1 domain of WWOX binds to PPXY motifs within WBP1 and WBP2 in a physiologically relevant manner, the WW2 domain exhibits no affinity toward any of these PPXY motifs. Importantly, our data suggest that while R25/W44 residues located within the binding pocket of a triple-stranded β-fold of WW1 domain are critical for the recognition of PPXY ligands, they are replaced by the chemically distinct E66/Y85 duo at structurally equivalent positions within the WW2 domain, thereby accounting for its failure to bind PPXY ligands. Predictably, not only does the introduction of E66R/Y85W double substitution within the WW2 domain result in gain of function but the resulting engineered domain, hereinafter referred to as WW2_RW, also appears to be a much stronger binding partner of WBP1 and WBP2 than the wild-type WW1 domain. We also show that while the WW1 domain is structurally disordered and folds upon ligand binding, the WW2 domain not only adopts a fully structured conformation but also aids stabilization and ligand binding to WW1 domain. This salient observation implies that the WW2 domain likely serves as a chaperone to augment the physiological function of WW1 domain within WWOX. Collectively, our study lays the groundwork for understanding the molecular basis of a key protein-protein interaction pertinent to human health and disease.
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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.