ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2021
OTUD7B Deubiquitinates LSD1 to Govern Its Binding Partner Specificity, Homeostasis, and Breast Cancer Metastasis.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 85 citations in OpenAlex.
- Single-Cell Multiomics Reveals That OTUD7B Is a Central Driver of Epithelial Remodelling and the Immunosuppressive Microenvironment in Pancreatic Ductal Adenocarcinoma.Journal of cellular and molecular medicine · 2026Article
- Prognostic Significance of Deubiquitinase OTUD7B in NK/T-Cell Lymphoma.Asia-Pacific journal of clinical oncology · 2026Article
- Microglial Deubiquitinase OTUD7B Stabilizes STAT3 to Promote Neuroinflammation and Cognitive Decline in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cardiomyocyte-derived OTUD7B promotes cardiac hypertrophy by deubiquitinating SERCA2a.Theranostics · 2026Article
- OTU deubiquitinases as immune-circuit editors: from human immunopathology to therapeutic prioritization.Frontiers in immunology · 2026Review
- Research progress of OTUD7B: from structural function and disease mechanisms to clinical translation.Frontiers in immunology · 2026Review
- Histone lysine demethylases in breast cancer: molecular mechanisms, biological functions, and therapeutic intervention.Molecular cancer · 2025Review
- USP25 deubiquitinates cytosolic METTL3 to impede glioma proliferation via an m6A-independent pathway.iScience · 2025Article
- Corin: a dual inhibitor for KDM1A/HDAC1, suppresses hepatocellular carcinoma by triggering cuproptosis.Clinical and experimental medicine · 2025Article
- HSPB1/KDM1 A facilitates ANXA2 expression via hypomethylated DNA promoter to inhibit ferroptosis and enhance gemcitabine resistance in pancreatic cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- A Small-Molecule Compound Targeting Canine Mammary Cancer Regulates CXCL10 and MECOM Transcripts via Histone Modifications in CMT-N7.Animals : an open access journal from MDPI · 2025Article
- CoREST in pieces: Dismantling the CoREST complex for cancer therapy and beyond.Science advances · 2025Review
- The multifaceted role of post-translational modifications of LSD1 in cellular processes and disease pathogenesis.Genes & diseases · 2025Review
- LSD1 is a targetable vulnerability in gastric cancer harboring TP53 frameshift mutations.Clinical epigenetics · 2025Article
- OTUD7B Stabilization by METTL14-Mediated m6A Methylation Drives HIF-1Oncology research · 2025Article
- OTU deubiquitinases in cancer pathogenesis and precision therapy.American journal of cancer research · 2025Review
- OTUD7B is a new deubiquitinase targeting p53.Theranostics · 2025Article
- Pulrodemstat, a selective inhibitor of KDM1A, suppresses head and neck squamous cell carcinoma growth by triggering apoptosis.BMC pharmacology & toxicology · 2024Article
- METTL14 suppresses the expression of YAP1 and the stemness of triple-negative breast cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Strategies that regulate LSD1 for novel therapeutics.Acta pharmaceutica Sinica. B · 2024Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Genomic amplification of OTUD7B is frequently found across human cancers. But its role in tumorigenesis is poorly understood. Lysine-specific demethylase 1 (LSD1) is known to execute epigenetic regulation by forming corepressor complex with CoREST/histone deacetylases (HDACs). However, the molecular mechanisms by which cells maintain LSD1/CoREST complex integrity are unknown. Here, it is reported that LSD1 protein undergoes K63-linked polyubiquitination. OTUD7B is responsible for LSD1 deubiquitination at K226/277 residues, resulting in dynamic control of LSD1 binding partner specificity and cellular homeostasis. OTUD7B deficiency increases K63-linked ubiquitination of LSD1, which disrupts LSD1/CoREST complex formation and targets LSD1 for p62-mediated proteolysis. Consequently, OTUD7B deficiency impairs genome-wide LSD1 occupancy and enhances the methylation of H3K4/H3K9, therefore profoundly impacting global gene expression and abrogating breast cancer metastasis. Moreover, physiological fluctuation of OTUD7B modulates cell cycle-dependent LSD1 oscillation, ensuring the G1/S transition. Both OTUD7B and LSD1 proteins are overpresented in high-grade or metastatic human breast cancer, while dysregulation of either protein is associated with poor survival and metastasis. Thus, OTUD7B plays a unique partner-switching role in maintaining the integrity of LSD1/CoREST corepressor complex, LSD1 turnover, and breast cancer metastasis.
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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.