Akoulitchev S, Reinberg D
Howard Hughes Medical Institute, Division of Nucleic Acids Enzymology, Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854-5635 USA.
Genes Dev. 1998 Nov 15;12(22):3541-50. doi: 10.1101/gad.12.22.3541.
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.
TFIIH是一种多亚基复合物，包含ATP酶、解旋酶和激酶活性。在功能上，TFIIH与RNA聚合酶II（RNAPII）介导的转录以及核苷酸切除修复有关。细胞周期蛋白依赖性激酶家族成员CDK7是TFIIH的激酶亚基。在遗传学上，CDK7同源物与酿酒酵母中的转录以及粟酒裂殖酵母中的有丝分裂调控有关。在此我们表明，在有丝分裂过程中，TFIIH的CDK7亚基和RNAPII的最大亚基会发生过度磷酸化。MPF诱导的CDK7磷酸化导致与TFIIH相关的激酶和转录活性受到抑制。TFIIH的负调控和正调控需要CDK7的T环内发生磷酸化。我们的数据确立了TFIIH及其亚基CDK7是转录调控与细胞周期之间的直接联系。
