Human mediator kinase subunit CDK11 plays a negative role in viral activator VP16-dependent transcriptional regulation

Genes Cells. 2008 Aug;13(8):817-26. doi: 10.1111/j.1365-2443.2008.01208.x. Epub 2008 Jun 21.

Abstract

Mediator is an essential transcriptional cofactor of RNA polymerase II (Pol II) in eukaryotes. This cofactor is a large complex containing up to 30 subunits and consisting of four modules: head, middle, tail, and CDK/Cyclin. Generally, Mediator connects transcriptional regulators, cofactors, chromatin regulators, and chromatin remodellers, with the pre-initiation complex to provide a platform for the assembly of these factors. Many previous studies have revealed that CDK8, a subunit of the CDK/Cyclin module, is one of the key subunits mediating the pivotal roles of Mediator in transcriptional regulation. In addition to CDK8, CDK11 is conserved among vertebrates as a Mediator subunit and closely resembles CDK8. While the role of CDK8 has been studied extensively, little is known of the role of CDK11 in Mediator. We purified human CDK11 (hCDK11)-containing protein complexes from an epitope-tagged hCDK11-expressing HeLa cell line and found that hCDK11 could independently form Mediator complexes devoid of human CDK8 (hCDK8). To investigate the in vivo transcriptional activity of the complex, we employed a luciferase assay. Although hCDK11 has nearly 80% amino acid sequence identity to hCDK8, siRNA-knockdown study revealed that hCDK8 and hCDK11 possess opposing functions in viral activator VP16-dependent transcriptional regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cyclin-Dependent Kinase 8
  • Cyclin-Dependent Kinases / chemistry
  • Cyclin-Dependent Kinases / metabolism*
  • HeLa Cells
  • Herpes Simplex Virus Protein Vmw65 / genetics*
  • Humans
  • Molecular Sequence Data

Substances

  • Herpes Simplex Virus Protein Vmw65
  • CDK11a protein, human
  • CDK8 protein, human
  • Cyclin-Dependent Kinase 8
  • Cyclin-Dependent Kinases