ArticlePLoS genetics2017
Dysregulation of INF2-mediated mitochondrial fission in SPOP-mutated prostate cancer.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed.
- Not only as a Cullin3 ligase adaptor, SPOP may also act as a molecular bridge.Genes & diseases · 2027Review
- SPOP-mediated K27-linked non-degradative ubiquitination of KCNN3 suppressing HCC progression via the CTCF-SATB1 axis.Cell death & disease · 2026Article
- Molecular insights for the tumor suppressor role of SPOP in prostate cancer.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Modulation of mitochondrial quality control in sepsis by traditional Chinese medicine: mechanistic insights and translational perspectives.Frontiers in pharmacology · 2026Review
- Disulfidptosis-related genes signature predicts prognosis and immune microenvironment in colon cancer.Frontiers in molecular biosciences · 2026Article
- Glucose Deprivation-Induced Disulfidptosis via the SLC7A11-INF2 Axis: Pan-Cancer Prognostic Exploration and Therapeutic Validation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cancer-associated SPOP mutations enlarge nuclear size and facilitate nuclear envelope rupture upon farnesyltransferase inhibitor treatment.The Journal of clinical investigation · 2025Article
- LMNB2-mediated high PD-L1 transcription triggers the immune escape of hepatocellular carcinoma.Cell death discovery · 2025Article
- Sequence rules for a long SPOP-binding degron required for protein ubiquitylation.The Biochemical journal · 2025Article
- Mitochondria-Associated Membranes: A Key Point of Neurodegenerative Diseases.CNS neuroscience & therapeutics · 2025Review
- Challenges and opportunities for the diverse substrates of SPOP E3 ubiquitin ligase in cancer.Theranostics · 2025Review
- Rewired glycolysis by DTL accelerates oncometabolite L-lactate generation to promote breast cancer progression.Frontiers in oncology · 2025Article
- INF2 mutations cause kidney disease through a gain-of-function mechanism.Science advances · 2024Article
- Phosphorylation of INF2 by AMPK promotes mitochondrial fission and oncogenic function in endometrial cancer.Cell death & disease · 2024Article
- The DNA-dependent protein kinase catalytic subunit promotes sepsis-induced cardiac dysfunction through disrupting INF-2-dependent mitochondrial dynamics.International journal of medical sciences · 2024Article
- Role of actin-binding proteins in prostate cancer.Frontiers in cell and developmental biology · 2024Review
- Fasting regulates mitochondrial function through lncRNA PRKCQ-AS1-mediated IGF2BPs in papillary thyroid carcinoma.Cell death & disease · 2023Article
- FBXO7, a tumor suppressor in endometrial carcinoma, suppresses INF2-associated mitochondrial division.Cell death & disease · 2023Article
- SPOP mutations promote tumor immune escape in endometrial cancer via the IRF1-PD-L1 axis.Cell death and differentiation · 2023Article
- Broadening horizons: the contribution of mitochondria-associated endoplasmic reticulum membrane (MAM) dysfunction in diabetic kidney disease.International journal of biological sciences · 2023Review
Corrections and comments
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Authors and funding
18 authors.
Funding
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Abstract
Next-generation sequencing of the exome and genome of prostate cancers has identified numerous genetic alternations. SPOP (Speckle-type POZ Protein) was one of the most frequently mutated genes in primary prostate cancer, suggesting SPOP is a potential driver of prostate cancer development and progression. However, how SPOP mutations contribute to prostate cancer pathogenesis remains poorly understood. SPOP acts as an adaptor protein of the CUL3-RBX1 E3 ubiquitin ligase complex that generally recruits substrates for ubiquitination and subsequent degradation. ER-localized isoform of the formin protein inverted formin 2 (INF2) mediates actin polymerization at ER-mitochondria intersections and facilitates DRP1 recruitment to mitochondria, which is a critical step in mitochondrial fission. Here, we revealed that SPOP recognizes a Ser/Thr (S/T)-rich motif in the C-terminal region of INF2 and triggers atypical polyubiquitination of INF2. These ubiquitination modifications do not lead to INF2 instability, but rather reduces INF2 localization in ER and mitochondrially associated DRP1 puncta formation, therefore abrogates its ability to facilitate mitochondrial fission. INF2 mutant escaping from SPOP-mediated ubiquitination is more potent in prompting mitochondrial fission. Moreover, prostate cancer-associated SPOP mutants increase INF2 localization in ER and promote mitochondrial fission, probably through a dominant-negative effect to inhibit endogenous SPOP. Moreover, INF2 is important for SPOP inactivation-induced prostate cancer cell migration and invasion. These findings reveal novel molecular events underlying the regulation of INF2 function and localization, and provided insights in understanding the relationship between SPOP mutations and dysregulation of mitochondrial dynamics in prostate cancer.
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