biostudies-literatureUnknown46(1)Liu ZYThe transcription factor STAT3 is a promising target for the treatment of non-small cell lung cancer (NSCLC). STAT3 activity is mainly dependent on phosphorylation at tyrosine 705 (pSTAT3-Y705), but the modulation on pSTAT3-Y705 is elusive. By screening a library of deubiquitinases (Dubs), we found that the Otub1 increases STAT3 transcriptional activity. As a Dub, Otub1 binds to pSTAT3-Y705 and specifically abolishes its K48-linked ubiquitination, therefore preventing its degradation and promoting NSCLC cell survival. The Otub1/pSTAT3-Y705 axis could be a potential target for the treatment of NSCLC. To explore this concept, we screen libraries of FDA-approved drugs and natural products based on STAT3-recognition element-driven luciferase assay, from which crizotinib is found to block pSTATActa pharmacologica Sinica184-195https://www.ebi.ac.uk/biostudies/studies/S-EPMC11697133biostudies-literatureInhibiting the Otub1/phosphorylated STAT3 axis for the treatment of non-small cell lung cancer.PMC11697133He YMOu YJJiang QYLi PFMao XLZhang YWRen YZhuang HXLiu ZYfalseInhibiting the Otub1/phosphorylated STAT3 axis for the treatment of non-small cell lung cancer.The transcription factor STAT3 is a promising target for the treatment of non-small cell lung cancer (NSCLC). STAT3 activity is mainly dependent on phosphorylation at tyrosine 705 (pSTAT3-Y705), but the modulation on pSTAT3-Y705 is elusive. By screening a library of deubiquitinases (Dubs), we found that the Otub1 increases STAT3 transcriptional activity. As a Dub, Otub1 binds to pSTAT3-Y705 and specifically abolishes its K48-linked ubiquitination, therefore preventing its degradation and promoting NSCLC cell survival. The Otub1/pSTAT3-Y705 axis could be a potential target for the treatment of NSCLC. To explore this concept, we screen libraries of FDA-approved drugs and natural products based on STAT3-recognition element-driven luciferase assay, from which crizotinib is found to block pSTAT2025-01-01T00:00:00Z2025 Jan2026-06-06T19:56:36.893Z2026-06-04T03:12:27.452ZS-EPMC116971333919866310.1038/s41401-024-01366-w