Cyclin-dependent kinase 7–cyclin H–MAT1 complex (CDK7–Cyclin H–MAT1 complex (also called CAK))

The CDK7–Cyclin H–MAT1 complex is a heterotrimeric protein complex known as the CDK-activating kinase (CAK)[1][2][3]. CDK7 is a cyclin-dependent kinase that, when assembled with cyclin H and the RING-finger protein MAT1, becomes essential for two major cellular processes: progression through the cell cycle and regulation of gene transcription. Within CAK, CDK7 can directly phosphorylate and activate other CDKs, enabling proper cell division[2][3][4]. As a component of the general transcription factor TFIIH, the complex phosphorylates the C-terminal domain of RNA polymerase II to initiate transcription and facilitate mRNA synthesis[1][2][3][5][6]. MAT1 is required for maximal activation and the stabilization of the complex[1][3][6]. The CAK complex has a unique regulatory mechanism involving dual phosphorylation of CDK7’s activation segment and extensive protein-protein interactions, distinguishing it from other CDK/cyclin complexes and making it a target of interest in cancer therapy[1][4]. Inhibition leads to coordinated blockade of cell proliferation and transcription, but brings potential risks of broad toxicity due to its pivotal roles[1][4].

Other names

CAK complexCDK7-Cyclin H-MAT1TFIIH-associated CAKCDK7 complex

Inhibition of kinase activity (blocks phosphorylation of substrates); Blocking cell cycle progression; Suppression of transcriptional activation (via RNA polymerase II inhibition)