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The molecular mechanism of mitotic inhibition of TFIIH is mediated by phosphorylation of CDK7.
S Akoulitchev, D Reinberg
Genes & development 1998 Nov 15
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TFIIH is a multisubunit complex, containing ATPase, helicases, and kinase activities. Functionally, TFIIH has been implicated in transcription by RNA polymerase II (RNAPII) and in nucleotide excision repair. A member of the cyclin-dependent kinase family, CDK7, is the kinase subunit of TFIIH. Genetically, CDK7 homologues have been implicated in transcription in Saccharomyces cerevisiae, and in mitotic regulation in Schizosaccharomyces pombe. Here we show that in mitosis the CDK7 subunit of TFIIH and the largest subunit of RNAPII become hyperphosphorylated. MPF-induced phosphorylation of CDK7 results in inhibition of the TFIIH-associated kinase and transcription activities. Negative and positive regulation of TFIIH requires phosphorylation within the T-loop of CDK7. Our data establishes TFIIH and its subunit CDK7 as a direct link between the regulation of transcription and the cell cycle.
Citation
S Akoulitchev, D Reinberg.
The molecular mechanism of mitotic inhibition of TFIIH is mediated by phosphorylation of CDK7.
Genes & development.
1998 Nov 15;12(22):3541-50
Mesh Tags
Amino Acid Sequence
Cell Cycle
Cyclin-Dependent Kinases
Flow Cytometry
HeLa Cells
Humans
Macromolecular Substances
Mitosis
Molecular Sequence Data
Mutation
Phosphorylation
Protein Kinases
Protein Serine-Threonine Kinases
Saccharomyces cerevisiae Proteins
Sequence Analysis
TATA-Binding Protein Associated Factors
Transcription Factor TFIID
Transcription Factor TFIIH
Transcription Factors
Transcription Factors, TFII
Transcription, Genetic
Cyclin-Dependent Kinase-Activating Kinase
Substances
Macromolecular Substances
Saccharomyces cerevisiae Proteins
TAF6 protein, S cerevisiae
TATA-Binding Protein Associated Factors
Transcription Factor TFIID
Transcription Factors
Transcription Factors, TFII
Transcription Factor TFIIH
Protein Kinases
carboxy-terminal domain kinase
Protein Serine-Threonine Kinases
Cyclin-Dependent Kinases
Cyclin-Dependent Kinase-Activating Kinase
CDK7 protein, human
PMID: 9832506
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