Chemical inhibition of the TFIIH-associated kinase Cdk7/Kin28 does not impair global mRNA synthesis

Elenita I. Kanin, Ryan T. Kipp, Charles Kung, Matthew Slattery, Agnes Viale, Steven Hahn, Kevan M. Shokat, Aseem Z. Ansari

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

The process of gene transcription requires the recruitment of a hypophosphorylated form of RNA polymerase II (Pol II) to a gene promoter. The TFIIH-associated kinase Cdk7/Kin28 hyperphosphorylates the promoter-bound polymerase; this event is thought to play a crucial role in transcription initiation and promoter clearance. Studies using temperature-sensitive mutants of Kin28 have provided the most compelling evidence for an essential role of its kinase activity in global mRNA synthesis. In contrast, using a small molecule inhibitor that specifically inhibits Kin28 in vivo, we find that the kinase activity is not essential for global transcription. Unlike the temperature-sensitive alleles, the small-molecule inhibitor does not perturb protein-protein interactions nor does it provoke the disassociation of TFIIH from gene promoters. These results lead us to conclude that other functions of TFIIH, rather than the kinase activity, are critical for global gene transcription.

Original languageEnglish (US)
Pages (from-to)5812-5817
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number14
DOIs
StatePublished - Apr 3 2007

Keywords

  • CTD kinase
  • Chemical genetics
  • TFIIH disassembly

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