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Adv."],"published-print":{"date-parts":[[2026,7,3]]},"abstract":"<jats:p>Targeting transcriptional condensates is an emerging paradigm for cancer therapy. A key player is the transcriptional coactivator YAP (Yes-associated protein), which drives tumor-specific programs that fuel tumor progression and therapeutic resistance. Cyclin K, partnered with cyclin-dependent kinases (CDKs) CDK12\/CDK13, is essential for transcription elongation, but its role in specific oncogenic programs was unclear. Here, we identify Cyclin K as an essential vulnerability across multiple cancer types. The CDK12\/Cyclin K complex binds YAP via Cyclin K and forms a regulatory condensate to bridge YAP phosphorylation by CDK12. Such a phosphorylation at threonine-398 impedes YAP inhibition by its canonical LATS kinases, stabilizes YAP, and enables its further condensation with TEAD4 to stimulate YAP oncogenic activity. Coexpression of CDK12\/Cyclin K and YAP predicts sensitivity to Cyclin K inhibitors in hepatocellular carcinoma cells and patient-derived xenografts. Thus, we define CDK12\/Cyclin K as a critical regulator of YAP-driven transcriptional addiction and a biomarker for patient stratification who mostly benefit from therapies targeting the CDK12\/Cyclin K\u2013YAP axis.<\/jats:p>","DOI":"10.1126\/sciadv.aec6492","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T17:58:28Z","timestamp":1783101508000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Cyclin K condensates bridge CDK12 to phosphorylate and drive oncogenic YAP activation in hepatocellular carcinoma"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6078-672X","authenticated-orcid":true,"given":"Yang","family":"Sun","sequence":"first","affiliation":[{"name":"Laboratory of Targeted Therapy and Precision Medicine, Department of Clinical Laboratory, Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, Shanghai, 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