CDK7
Description
The CDK7 (cyclin dependent kinase 7) is a protein-coding gene located on chromosome 5.
Cyclin-dependent kinase 7, or cell division protein kinase 7, is an enzyme that in humans is encoded by the CDK7 gene. The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK family members are highly similar to the gene products of Saccharomyces cerevisiae cdc28, and Schizosaccharomyces pombe cdc2, and are known to be important regulators of cell cycle progression. This protein forms a trimeric complex with cyclin H and MAT1, which functions as a Cdk-activating kinase (CAK). It is an essential component of the transcription factor TFIIH, that is involved in transcription initiation and DNA repair. This protein is thought to serve as a direct link between the regulation of transcription and the cell cycle.
== Clinical significance e.g. cancer == Given that CDK7 is involved in two important regulation roles, it's expected that CDK7 regulation may play a role in cancerous cells. Cells from breast cancer tumors were found to have elevated levels of CDK7 and Cyclin H when compared to normal breast cells. It was also found that the higher levels were generally found in ER-positive breast cancer.
CDK7 is a serine/threonine kinase involved in both cell cycle control and RNA polymerase II-mediated transcription. It functions as the catalytic subunit of the CDK-activating kinase (CAK) complex, which activates cyclin-associated kinases CDK1, CDK2, CDK4, and CDK6 through phosphorylation, thereby regulating cell cycle progression. CAK, when associated with the TFIIH basal transcription factor, activates RNA polymerase II by phosphorylating its C-terminal domain (CTD), enabling transcription elongation. CDK7 also plays a role in transcription initiation by phosphorylating POLR2A, leading to its dissociation from DNA. Interestingly, its expression and activity remain constant throughout the cell cycle. Upon DNA damage, CDK7 triggers p53 activation through phosphorylation, but is subsequently inactivated by p53, creating a feedback loop that can result in cell cycle arrest, transcription suppression, cell recovery, or apoptosis. CDK7 is also crucial for DNA-bound peptides-mediated transcription and cellular growth inhibition. It primarily forms the CAK complex with cyclin-H (CCNH) and MAT1 and can further associate with the TFIIH basal transcription factor, making the complex sensitive to UV light. The CAK complex binds to p53 in response to DNA damage. CDK7 interacts with various proteins including CDK2, SF1/NR5A1, PUF60, PRKCI, and HINT1.
CDK7 is also known as CAK, CAK1, CDKN7, HCAK, MO15, STK1, p39MO15.
