CDK12/CDK13 inhibition disrupts transcriptional elongation and fork progression in glioblastoma

ABSTRACT: Glioblastomas are the most prevalent and aggressive malignant brain tumors, characterized by hypertranscription and dependence on neurodevelopmental transcription factors. The transcriptional cycle is regulated by phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (RNAPII) by transcriptional cyclin-dependent kinases (tCDK), including CDK7, CDK9, CDK12, and CDK13. Here we find that glioblastoma stem cells (GSC) are selectively sensitive to CDK12/CDK13 inhibition, whereas CDK7 and CDK9 inhibition cause non-specific cytotoxicity. This selective targeting halts GSC and organoid proliferation, curtails GSC invasion and suppresses tumor growth in a xenograft mouse model. In GSCs, CDK12/CDK13 inhibition leads to a rapid and genome-wide loss of serine-2 phosphorylation (pSer2) of

SUBMITTER: Silje Lier 

PROVIDER: S-SCDT-10_1038-S44321-026-00393-W | biostudies-other |

REPOSITORIES: biostudies-other