ArticleCell death and differentiation2021
USP42 drives nuclear speckle mRNA splicing via directing dynamic phase separation to promote tumorigenesis.
Article in Cell death and differentiation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 62 citations in OpenAlex.
- The deubiquitinating enzyme USP42 promotes lung adenocarcinoma progression through PTGS2.Journal of molecular histology · 2026Article
- Liquid-liquid phase separation in cancer: oncogenic roles, therapeutic potential, and epigenetic regulation.Molecular biology reports · 2026Review
- A framework for the exploration of subcellular compartmentalization of RNA-binding proteins.Nature communications · 2026Article
- Exploring Disordered Regions of Human Spliceosome Proteins.The journal of physical chemistry letters · 2026Article
- SRSF9 mediates oncogenic RNA splicing of SLC37A4 via liquid-liquid phase separation to promote oral cancer progression.Journal of advanced research · 2026Article
- The COX-2 Inhibitor Celecoxib Sensitizes Nasopharyngeal Carcinoma Cells to Ferroptosis.Current cancer drug targets · 2026Article
- Deep learning model of post-translational modification regulating liquid-liquid phase separation.Communications chemistry · 2025Article
- Proteome-wide computational analyses reveal links between protein condensate formation and RNA biology.Science advances · 2025Article
- Alternative Splicing: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets.MedComm · 2025Review
- Deubiquitinating enzyme USP42 promotes breast cancer progression by inhibiting JNK/p38-mediated apoptosis.Scientific reports · 2025Article
- Biomolecular condensates in lung cancer: from molecular mechanisms to therapeutic targeting.Cell death discovery · 2025Review
- Periplocin potentiates ferroptotic cell death in non-small cell lung cancer by inducing the degradation of Nrf2.Cancer cell international · 2025Article
- Membraneless Organelles and Phase Separation in Tumours: Mechanisms and Prospects.Cell proliferation · 2025Review
- FGF2 Mediated USP42-PPARγ Axis Activation Ameliorates Liver Oxidative Damage and Promotes Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Nuclear Condensates of WW Domain-Containing Adaptor With Coiled-Coil Regulate Mitophagy via Alternative Splicing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Oncogenic RIT1 mutations confer ferroptosis vulnerability in lung adenocarcinoma.Biology direct · 2025Article
- Protein quality control machinery: regulators of condensate architecture and functionality.Trends in biochemical sciences · 2025Review
- USP39 phase separates into the nucleolus and drives lung adenocarcinoma progression by promoting GLI1 expression.Cell communication and signaling : CCS · 2025Article
- Targeting USP42 induces DNA damage and inhibits cell growth in prostate cancer.Frontiers in molecular biosciences · 2025Article
- CLK2 Condensates Reorganize Nuclear Speckles and Induce Intron Retention.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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15 authors at 1 institution in 1 country.
Funding
Abstract
Liquid-liquid phase separation is considered a generic approach to organize membrane-less compartments, enabling the dynamic regulation of phase-separated assemblies to be investigated and pivotal roles of protein posttranslational modifications to be demonstrated. By surveying the subcellular localizations of human deubiquitylases, USP42 was identified to form nuclear punctate structures that are associated with phase separation properties. Bioinformatic analysis demonstrated that the USP42 C-terminal sequence was intrinsically disordered, which was further experimentally confirmed to confer phase separation features. USP42 is distributed to SC35-positive nuclear speckles in a positively charged C-terminal residue- and enzymatic activity-dependent manner. Notably, USP42 directs the integration of the spliceosome component PLRG1 into nuclear speckles, and its depletion interferes with the conformation of SC35 foci. Functionally, USP42 downregulation deregulates multiple mRNA splicing events and leads to deterred cancer cell growth, which is consistent with the impact of PLRG1 repression. Finally, USP42 expression is strongly correlated with that of PLRG1 in non-small-cell lung cancer samples and predicts adverse prognosis in overall survival. As a deubiquitylase capable of dynamically guiding nuclear speckle phase separation and mRNA splicing, USP42 inhibition presents a novel anticancer strategy by targeting phase separation.
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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.