Cyclin-dependent kinase 7–Cyclin H complex (CDK7–Cyclin H)

The **Cyclin-dependent kinase 7–Cyclin H complex** (CDK7–Cyclin H) is a heterodimeric protein kinase complex fundamental to cell cycle progression and transcription regulation. CDK7, a member of the cyclin-dependent kinase family, requires association with Cyclin H (and a third subunit, MAT1, for full activity) to function as a CDK-activating kinase (CAK), phosphorylating and activating other CDKs that drive transitions in the eukaryotic cell cycle[1][2][3][6][7]. The complex is also a core component of the transcription factor IIH (TFIIH), regulating transcription initiation and DNA repair by phosphorylating the RNA polymerase II C-terminal domain (CTD)[1][2][3][6][7]. This dual role links transcriptional control and cell cycle regulation at the molecular level. Dysregulation or overexpression of components of this complex, particularly in breast and other cancers, has made it an attractive therapeutic target, with multiple kinase inhibitors under clinical investigation. The complex is structurally characterized by tight mutual interactions and unique regulatory features, including requirements for both subunit association and phosphorylation for full activation[1][2][3][6]. Safety concerns for emerging therapies include global effects on cell proliferation and transcription that may impact normal rapidly dividing cells.

Other names

CDK-activating kinase (CAK)Cyclin-dependent kinase 7–Cyclin H–MAT1 complex (for the full complex, sometimes referred to as CAK)Cell division protein kinase 7–Cyclin H

Inhibition of CDK7 kinase activity, leading to decreased phosphorylation of RNA polymerase II and down-regulation of transcription - Inhibition of CDK7, preventing activation of other CDKs involved in cell cycle progression