CDK7 Recombinant Protein

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. [provided by RefSeq, Jul 2008]

Function: Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription. Cyclin-dependent kinases (CDKs) are activated by the binding to a cyclin and mediate the progression through the cell cycle. Each different complex controls a specific transition between 2 subsequent phases in the cell cycle. Required for both activation and complex formation of CDK1/cyclin-B during G2-M transition, and for activation of CDK2/cyclins during G1-S transition (but not complex formation). CDK7 is the catalytic subunit of the CDK-activating kinase (CAK) complex. Phosphorylates SPT5/SUPT5H, SF1/NR5A1, POLR2A, p53/TP53, CDK1, CDK2, CDK4, CDK6 and CDK11B/CDK11. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation, thus regulating cell cycle progression. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminus domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Phosphorylation of POLR2A in complex with DNA promotes transcription initiation by triggering dissociation from DNA. 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. Ref.9 Ref.12 Ref.13 Ref.15 Ref.17 Ref.18 Ref.19 Ref.22 Ref.24 Ref.25 Ref.26 Ref.28 Ref.29 Ref.31

Catalytic activity: ATP + a protein = ADP + a phosphoprotein.ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate.

Enzyme regulation: Inactivated by phosphorylation. Repressed by roscovitine (seliciclib, CYC202), R547 (Ro-4584820) and SNS-032 (BMS-387032). The association of p53/TP53 to the CAK complex in response to DNA damage reduces kinase activity toward CDK2 and RNA polymerase II repetitive C-terminus domain (CTD), thus stopping cell cycle progression. The inactivation by roscovitine promotes caspase-mediated apoptosis in leukemic cells. Ref.12 Ref.32

Subunit structure: Associates primarily with cyclin-H (CCNH) and MAT1 to form the CAK complex. CAK can further associate with the core-TFIIH to form the TFIIH basal transcription factor; this complex is sensitive to UV light. The CAK complex binds to p53/TP53 in response to DNA damage. Interacts with CDK2, SF1/NR5A1, PUF60 and PRKCI. Ref.11 Ref.12 Ref.14 Ref.16 Ref.17 Ref.19 Ref.22

Subcellular location: Nucleus. Cytoplasm. Cytoplasm › perinuclear region. Note: Colocalizes with PRKCI in the cytoplasm and nucleus. Translocates from the nucleus to cytoplasm and perinuclear region in response to DNA-bound peptides. Ref.16 Ref.29

Tissue specificity: Ubiquitous.

Induction: Repressed by DNA-bound peptides. Ref.12 Ref.29 Ref.32

Post-translational modification: Phosphorylation of Ser-164 during mitosis inactivates the enzyme. Phosphorylation of Thr-170 is required for activity. Phosphorylated at Ser-164 and Thr-170 by CDK2. Ref.10 Ref.15 Ref.39

Sequence similarities: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.Contains 1 protein kinase domain.