Cyclin-dependent kinase 7 (CDK7) is a serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription. It is activated by binding to a cyclin; binding to a different cyclin and phosphorylation of another kinase progresses the cell cycle. CDK7 binds cyclin-B and phosphorylates CDK1 during G2-M transition, and phosphorylates CDK2 and binds to cyclins during G1-S transition [, ]. CDK7 phosphorylates and activates p53 following DNA damage [], but CDK7 is then inactivated by p53, which arrests the cell cycle, allowing the cell to recover or undergo apoptosis []. CDK7 is also the catalytic subunit of the CDK-activating kinase (CAK) complex, which also contains cyclin-H (CCNH) and MAT1 [, ]. In turn, the CAK associates with the core-TFIIH to form the TFIIH basal transcription factor [].This entry includes CDK7 from animals, Kin28 from budding yeasts and Crk1 (also known as Mcs6) from fission yeasts. S. pombe possesses two CAKs, the nonessential Csk1 and the essential Mcs6 kinases, corresponding to the yeast Cak1 and the metazoan CDK7, respectively. Mcs6 modulates gene expression through both its CAK and CTD kinase activities []. Kin28 is the closest homologue of CDK7 from budding yeasts. It forms a complex with Ccl1 and Tfb3. This complex associate with TFIIH for transcription regulating activity, but does not display CAK activity []. Instead, Cak1, a single-subunit kinase distantly related to Cdk, catalyzes Cdk activation at both transitions of the budding yeast cell cycle [].
MAT1/Tfb3 acts as component of the general transcription and DNA repair factor IIH (TFIIH), which is essential for both basal and activated transcription, and is involved in nucleotide excision repair (NER) of damaged DNA []. It is a RING finger protein with a characteristic C3HC4 motif located in the N-terminal domain. MAT1/Tfb3 stabilises the cyclin H-CDK7 complex to form a functional CDK-activating kinase (CAK) enzymatic complex which then goes on to activate many of the CDK enzymes intimately involved in the cell cycle []. CDK7 forms a stable complex with cyclin H and MAT1/Tfb3 in vivo only when phosphorylated on either one of two residues (Ser164 or Thr170) in its T-loop. The requirement for MAT1/Tfb3 for the activation of CAK can be by-passed by the phosphorylation of CDK7 on the T-loop. The two mechanisms for CDK7 complex stabilisation and activation (MAT1 addition and T-loop phosphorylation), which can operate independently in vitro, actually cooperate under physiological conditions to maintain complex integrity. With prolonged exposure to elevated temperature, dissociation to monomeric subunits occurs in vivo when CDK7 is dephosphorylated, even in the presence of MAT1/Tfb3 [].
MAT1 (menage a trois 1) is a RING finger protein with a characteristic C3HC4 motif located in the N-terminal domain. This entry represents the central region of MAT1. MAT1 stabilises the cyclin H-CDK7 complex to form a functional CDK-activating kinase (CAK) enzymatic complex which then goes on to activate many of the CDK enzymes intimately involved in the cell cycle []. CDK7 forms a stable complex with cyclin H and MAT1 in vivo only when phosphorylated on either one of two residues (Ser164 or Thr170) in its T-loop. The requirement for MAT1 for the activation of CAK can be by-passed by the phosphorylation of CDK7 on the T-loop. The two mechanisms for CDK7 complex stabilisation and activation (MAT1 addition and T-loop phosphorylation), which can operate independently in vitro, actually cooperate under physiological conditions to maintain complex integrity. With prolonged exposure to elevated temperature, dissociation to monomeric subunits occurs in vivo when CDK7 is dephosphorylated, even in the presence of MAT1 []. The Cyclin H-MAT1-CDK7 complex also forms part of TFIIH, a multiprotein complex required for both transcription and DNA repair.
