ArticleNucleic acids research2023
A bio-orthogonal linear ubiquitin probe identifies STAT3 as a direct substrate of OTULIN in glioblastoma.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Deubiquitinase OTULIN dampens RIG-I-dependent antiviral signaling by removing linear ubiquitination from TRAF6.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- QSOX2-Mediated Disulfide Bond Modification Enhances Tumor Stemness and Chemoresistance by Activating TSC2/mTOR/c-Myc Feedback Loop in Esophageal Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Spatiotemporal Regulation of STING Activity by Linear Ubiquitination Governs Antiviral Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Dissecting the dual role of OTU family proteins in tumor progression and immune escape.Frontiers in immunology · 2025Review
- Inhibiting the Otub1/phosphorylated STAT3 axis for the treatment of non-small cell lung cancer.Acta pharmacologica Sinica · 2025Article
- Deciphering Key Regulatory Roles of Linear Ubiquitination in Cell Fate Determination and Disease.Research (Washington, D.C.) · 2025Review
- OTULIN confers cisplatin resistance in osteosarcoma by mediating GPX4 protein homeostasis to evade the mitochondrial apoptotic pathway.Journal of experimental & clinical cancer research : CR · 2024Article
- Met1-linked ubiquitination in cell signaling regulation.Biophysics reports · 2024Article
- OTUD4 promotes the progression of glioblastoma by deubiquitinating CDK1 and activating MAPK signaling pathway.Cell death & disease · 2024Article
- Mechanisms underlying linear ubiquitination and implications in tumorigenesis and drug discovery.Cell communication and signaling : CCS · 2023Review
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While linear ubiquitin plays critical roles in multiple cell signaling pathways, few substrates have been identified. Global profiling of linear ubiquitin substrates represents a significant challenge because of the low endogenous level of linear ubiquitination and the background interference arising from highly abundant ubiquitin linkages (e.g. K48- and K63-) and from the non-specific attachment of interfering proteins to the linear polyubiquitin chain. We developed a bio-orthogonal linear ubiquitin probe by site-specific encoding of a norbornene amino acid on ubiquitin (NAEK-Ub). This probe facilitates covalent labeling of linear ubiquitin substrates in live cells and enables selective enrichment and identification of linear ubiquitin-modified proteins. Given the fact that the frequent overexpression of the linear linkage-specific deubiquitinase OTULIN correlates with poor prognosis in glioblastoma, we demonstrated the feasibility of the NAEK-Ub strategy by identifying and validating substrates of linear ubiquitination in patient-derived glioblastoma stem-like cells (GSCs). We identified STAT3 as a bona fide substrate of linear ubiquitin, and showed that linear ubiquitination negatively regulates STAT3 activity by recruitment of the phosphatase TC-PTP to STAT3. Furthermore, we demonstrated that preferential expression of OTULIN in GSCs restricts linear ubiquitination on STAT3 and drives persistent STAT3 signaling, and thereby maintains the stemness and self-renewal of GSCs.
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