Recombinant Human Cyclin-dependent kinase 7 (CDK7)

Function

Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription (PubMed:9852112, PubMed:19136461, PubMed:26257281, PubMed:28768201). As a cyclin-dependent kinase, CDK7 is activated by the binding to cyclin-H/CCNH and the CDK-activating kinase assembly factor MAT1 (PubMed:41100585). Catalytic subunit of the CDK-activating kinase (CAK) complex, a master regulator of CDK activity by catalyzing the activating threonine phosphorylation of CDKs (PubMed:41100585). CAK activates major mediators of cell cycle control, including CDK1, CDK2, CDK4 and CDK6, and plays a key role in regulating cell cycle progression (PubMed:41100585). CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the CTD of POLR2A, allowing its escape from the promoter and elongation of the transcripts (PubMed:9852112). Initiates transcription by RNA polymerase II by mediating phosphorylation of POLR2A at 'Ser-5' of the repetitive C-terminal domain (CTD) when POLR2A is in complex with DNA, promoting dissociation from DNA and initiation (PubMed:19136461, PubMed:26257281, PubMed:28768201). Phosphorylates SPT5/SUPT5H, SF1/NR5A1, POLR2A, p53/TP53, CDK1, CDK2, CDK4, CDK6 and CDK11B/CDK11 (PubMed:9372954, PubMed:9840937, PubMed:19136461, PubMed:26257281, PubMed:28768201, PubMed:41100585, PubMed:41100585). Its expression and activity are constant throughout the cell cycle. Upon DNA damage, triggers p53/TP53 activation by phosphorylation, but is inactivated in turn by p53/TP53; this feedback loop may lead to an arrest of the cell cycle and of the transcription, helping in cell recovery, or to apoptosis. Required for DNA-bound peptides-mediated transcription and cellular growth inhibition

Subcellular Location

Nucleus; Cytoplasm; Cytoplasm, perinuclear region

Tissue Specificity

Ubiquitous

Subunit

Component of the CDK-activating kinase (CAK) complex, consisting of CDK7, cyclin-H/CCNH and MAT1, which is a master regulator of CDK activity (PubMed:41100585). CAK binds to both free CDK2 and cyclin-bound CDK2, with a higher affinity for the cyclin-bound form (PubMed:41100585). CAK can further associate with the core-TFIIH to form the TFIIH basal transcription factor (PubMed:9852112). The CAK complex binds to p53/TP53 in response to DNA damage. Interacts with CDK2, SF1/NR5A1, PUF60 and PRKCI. Interacts with HINT1 (PubMed:10958787)

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• Levedakou E.N. et al. Two novel human serine/threonine kinases with homologies to the cell cycle regulating Xenopus MO15, and NIMA kinases: cloning and characterization of their expression pattern. — Oncogene (1994)
• Darbon J.-M. et al. Cloning, expression and subcellular localization of the human homolog of p40MO15 catalytic subunit of cdk-activating kinase. — Oncogene (1994)
• Wu L. et al. Molecular cloning of the human CAK1 gene encoding a cyclin-dependent kinase-activating kinase. — Oncogene (1994)
• Kobelt D. et al. Human and Xenopus MO15 mRNA are highly conserved but show different patterns of expression in adult tissues. — Oncol. Rep. (1994)
• PubMed: CI-6QALB6QA9OC0B (JUL-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Fisher R.P. et al. A novel cyclin associates with MO15/CDK7 to form the CDK-activating kinase. — Cell (1994)