The cyclin-dependent kinase 8 module sterically blocks Mediator interactions with RNA polymerase II

Proc Natl Acad Sci U S A. 2006 Oct 24;103(43):15788-93. doi: 10.1073/pnas.0607483103. Epub 2006 Oct 16.

Abstract

CDK8 (cyclin-dependent kinase 8), along with CycC, Med12, and Med13, form a repressive module (the Cdk8 module) that prevents RNA polymerase II (pol II) interactions with Mediator. Here, we report that the ability of the Cdk8 module to prevent pol II interactions is independent of the Cdk8-dependent kinase activity. We use electron microscopy and single-particle reconstruction to demonstrate that the Cdk8 module forms a distinct structural entity that binds to the head and middle region of Mediator, thereby sterically blocking interactions with pol II.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclin-Dependent Kinase 8
  • Cyclin-Dependent Kinases / chemistry
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / metabolism*
  • Cyclin-Dependent Kinases / ultrastructure
  • Holoenzymes / chemistry
  • Holoenzymes / genetics
  • Holoenzymes / metabolism
  • Holoenzymes / ultrastructure
  • Microscopy, Electron
  • Models, Molecular
  • Protein Binding
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • RNA Polymerase II / chemistry
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism*
  • RNA Polymerase II / ultrastructure
  • Schizosaccharomyces / chemistry
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces / ultrastructure
  • Schizosaccharomyces pombe Proteins / chemistry
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Schizosaccharomyces pombe Proteins / ultrastructure

Substances

  • Holoenzymes
  • Schizosaccharomyces pombe Proteins
  • Cyclin-Dependent Kinase 8
  • Cyclin-Dependent Kinases
  • srb10 protein, S pombe
  • RNA Polymerase II