Inhibition of transcription by the trimeric cyclin-dependent kinase 7 complex.
Cyclin-dependent kinase 7 (CDK7) can be isolated as a subunit of a trimeric kinase complex functional in activation of the mitotic promoting factor. In this study, we demonstrate that the trimeric cdk-activating kinase (CAK) acts as a transcriptional repressor of class II promoters and show that repression results from CAK impeding the entry of RNA polymerase II and basal transcription factor IIF into a competent preinitiation complex. This repression is independent of CDK7 kinase activity. We find that the p36/MAT1 subunit of CAK is required for transcriptional repression and the repression is independent of the promoter used. Our results demonstrate a central role for CAK in regulation of messenger RNA synthesis by either inhibition of RNA polymerase II-catalyzed transcription or stimulation of transcription through association with basal transcription repair factor IIH.
Bochar
D A
DA
Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Pan
Z Q
ZQ
Knights
R
R
Fisher
R P
RP
Shilatifard
A
A
Shiekhattar
R
R
D001704:Biopolymers; D018844:Cyclin-Dependent Kinases; D006367:HeLa Cells; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000502:physiology*; D012319:RNA Polymerase II / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D019473:Transcription Factors, TFII; D014158:Transcription, Genetic / Q000502:physiology*; D000095043:Cyclin-Dependent Kinase-Activating Kinase
D001704:Biopolymers; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D017346:Protein Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases; D012319:RNA Polymerase II; C056604:transcription factor TFIIF; D000095043:Cyclin-Dependent Kinase-Activating Kinase; C000722416:CDK7 protein, human