ArticleMolecular cell2023
Higher-order SPOP assembly reveals a basis for cancer mutant dysregulation.
Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- Cancer treatment alters mutant selection in normal esophagus.Nature genetics · 2026Article
- SPOP-mediated ZMYND8 ubiquitination and phase separation exclusion drives mTOR inhibitor resistance in kidney cancer.Nature communications · 2026Article
- Large-scale quaternary structural transitions underlie gain of function of SPOP cancer mutations.Molecular cell · 2026Article
- MYC contributes to targeted therapy resistance in lung cancers driven by MET exon 14-skipping alteration.NPJ precision oncology · 2026Article
- Functional dissection ofProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Structures of ZYG11B-EloB-EloC-substrate complex reveal mechanisms of CRL2Nature communications · 2026Article
- Degrons and degradation signals beyond short linear motifs.Nature chemical biology · 2026Review
- CircLRBA Promotes Epithelial-Mesenchymal Transition, Immune Evasion, Chemoimmunotherapy Resistance and Metastasis Through Stabilizing Twist1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Molecular mechanisms by which C1orf112 promotes endometrial cancer progression and the development and validation of a clinical scoring model.Clinical epigenetics · 2025Article
- ENKD1 attenuates antibacterial immunity by facilitating TRIM21-mediated RUBCN degradation to suppress LC3-associated phagocytosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mutation-induced filaments of folded proteins are inert and non-toxic in a cellular system.Molecular systems biology · 2025Article
- The equilibrium between two quaternary assembly states determines the activity of SPOP and its cancer mutants.bioRxiv : the preprint server for biology · 2025Article
- Sequence rules for a long SPOP-binding degron required for protein ubiquitylation.The Biochemical journal · 2025Article
- Article
- Molecular determinants of condensate composition.Molecular cell · 2025Review
- Co-occurring BRCA2/SPOP Mutations Predict Exceptional Poly (ADP-ribose) Polymerase Inhibitor Sensitivity in Metastatic Castration-Resistant Prostate Cancer.European urology oncology · 2024Article
- Noncanonical assembly, neddylation and chimeric cullin-RING/RBR ubiquitylation by the 1.8 MDa CUL9 E3 ligase complex.Nature structural & molecular biology · 2024Article
- A conserved N-terminal motif of CUL3 contributes to assembly and E3 ligase activity of CRL3Nature communications · 2024Article
- Skraban-Deardorff intellectual disability syndrome-associated mutations in WDR26 impair CTLH E3 complex assembly.FEBS letters · 2024Article
- Structure and dynamics of a pentameric KCTD5/CUL3/Gβγ E3 ubiquitin ligase complex.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The speckle-type POZ protein (SPOP) functions in the Cullin3-RING ubiquitin ligase (CRL3) as a receptor for the recognition of substrates involved in cell growth, survival, and signaling. SPOP mutations have been attributed to the development of many types of cancers, including prostate and endometrial cancers. Prostate cancer mutations localize in the substrate-binding site of the substrate recognition (MATH) domain and reduce or prevent binding. However, most endometrial cancer mutations are dispersed in seemingly inconspicuous solvent-exposed regions of SPOP, offering no clear basis for their cancer-causing and peculiar gain-of-function properties. Herein, we present the first structure of SPOP in its oligomeric form, uncovering several new interfaces important for SPOP self-assembly and normal function. Given that many previously unaccounted-for cancer mutations are localized in these newly identified interfaces, we uncover molecular mechanisms underlying dysregulation of SPOP function, with effects ranging from gross structural changes to enhanced self-association, and heightened stability and activity.
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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.