CDKactivating

CDK activating refers to the process by which cyclin-dependent kinases (CDKs) are activated by phosphorylation in their activation loop, enabling full catalytic activity. This activation is essential for progression through the cell cycle and for transcription-related functions that depend on CDK activity.

CDKs gain partial activity by binding a cyclin partner; a conserved threonine residue in the activation loop must be phosphorylated by CDK-activating kinases (CAKs) to achieve full activity. Phosphorylation induces conformational changes that align catalytic residues and substrate binding sites, enabling efficient phosphorylation of target proteins involved in cell cycle transitions such as G1/S and G2/M.

In humans, the principal CDK-activating kinase activity is carried out by CDK7 together with Cyclin H and MAT1, forming the CAK complex. CDK7 is also a subunit of TFIIH, a general transcription factor complex involved in transcription initiation and nucleotide excision repair; as part of TFIIH, CDK7 contributes to phosphorylation of the RNA polymerase II C-terminal domain (CTD), linking cell cycle control to transcription regulation.

Organisms such as yeast use CAK enzymes that are homologous to CDK7 (for example Cak1 in Saccharomyces cerevisiae) to activate CDKs, and in many systems, activation and transcription-related roles are integrated through TFIIH components. While the exact composition and regulation of CAK activity vary by species, the core function—phosphorylating the activation loop of CDKs to promote cell cycle progression—appears conserved.

Clinical relevance: The CDK-activating axis is critical for cell proliferation, and dysregulation can contribute to cancer. CDK7 inhibitors are under investigation as anti-cancer therapies, reflecting the dual role of CDK7 in cell cycle control and transcription.