InterPro domain: IPR004575
General Information
- Identifier IPR004575
- Description Cdk-activating kinase assembly factor MAT1/Tfb3
- Number of genes 57
- Gene duplication stats Loading...
- Associated GO terms GO:0061575 GO:0045737 GO:0006289 GO:0005675
Abstract
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 [ 1 ]. 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 [ 2 ]. 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 [ 3 ].
1. Genes for Tfb2, Tfb3, and Tfb4 subunits of yeast transcription/repair factor IIH. Homology to human cyclin-dependent kinase activating kinase and IIH subunits. J. Biol. Chem. 272, 19319-27
2. Molecular structure of human TFIIH. Cell 102, 599-607
3. T-loop phosphorylation stabilizes the CDK7-cyclin H-MAT1 complex in vivo and regulates its CTD kinase activity. EMBO J. 20, 3749-59