ArticleCell death and differentiation2022
Deneddylation of PML/RARα reconstructs functional PML nuclear bodies via orchestrating phase separation to eradicate APL.
Article in Cell death and differentiation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Decoding Biomolecular Phase Separation: From Physiological Roles to Pathological Mechanisms and Therapeutic Biomaterials Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Advances in targeted therapies for pediatric tumors.Acta pharmacologica Sinica · 2026Article
- Decoding neddylation in malignancies: molecular mechanisms, biological functions, therapeutic resistance, and clinical potential.Cell death & disease · 2026Review
- Liquid-Liquid Phase Separation in Cancer Drug Resistance: Mechanisms and Therapeutic Opportunities.Oncology research · 2026Review
- Biomolecular phase separation in tumorigenesis: from aberrant condensates to therapeutic vulnerabilities.Molecular cancer · 2025Review
- Review
- Phase separation in mitochondrial fate and mitochondrial diseases.Proceedings of the National Academy of Sciences of the United States of America · 2025Review
- Diagnostic and Therapeutic Implications of the SUMOylation Pathway in Acute Myeloid Leukemia.Cancers · 2025Review
- CPSF6-RARγ interacts with histone deacetylase 3 to promote myeloid transformation in RARG-fusion acute myeloid leukemia.Nature communications · 2025Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- The Burgeoning Significance of Liquid-Liquid Phase Separation in the Pathogenesis and Therapeutics of Cancers.International journal of biological sciences · 2024Review
- Phase separations in oncogenesis, tumor progressions and metastasis: a glance from hallmarks of cancer.Journal of hematology & oncology · 2023Review
- Defining the condensate landscape of fusion oncoproteins.Nature communications · 2023Article
- VAPB-mediated ER-targeting stabilizes IRS-1 signalosomes to regulate insulin/IGF signaling.Cell discovery · 2023Article
- Biomolecular Condensates in Myeloid Leukemia: What Do They Tell Us?HemaSphere · 2023Review
- Review
- The Role of Phase-Separated Condensates in Fusion Oncoprotein-Driven Cancers.Annual review of cancer biology · 2023Article
- Liquid‒liquid phase separation: roles and implications in future cancer treatment.International journal of biological sciences · 2023Review
- Review
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute promyelocytic leukemia (APL) is driven by the oncoprotein PML/RARα, which destroys the architecture of PML nuclear bodies (NBs). PML NBs are critical to tumor suppression, and their disruption mediated by PML/RARα accelerates APL pathogenesis. However, the mechanisms of PML NB disruption remain elusive. Here, we reveal that the failure of NB assembly in APL results from neddylation-induced aberrant phase separation of PML/RARα. Mechanistically, PML/RARα is neddylated in the RARα moiety, and this neddylation enhances its DNA-binding ability and further impedes the phase separation of the PML moiety, consequently disrupting PML NB construction. Accordingly, deneddylation of PML/RARα restores its phase separation process to reconstruct functional NBs and activates RARα signaling, thereby suppressing PML/RARα-driven leukemogenesis. Pharmacological inhibition of neddylation by MLN4924 eradicates APL cells both in vitro and in vivo. Our work elucidates the neddylation-destroyed phase separation mechanism for PML/RARα-driven NB disruption and highlights targeting neddylation for APL eradication.
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