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

Authors
  • Tsutsui, Taiki
  • Umemura, Hiroyasu
  • Tanaka, Aki
  • Mizuki, Fumitaka
  • Hirose, Yutaka
  • Ohkuma, Yoshiaki
Type
Published Article
Journal
Genes to Cells
Publisher
Wiley (Blackwell Publishing)
Publication Date
Aug 01, 2008
Volume
13
Issue
8
Pages
817–826
Identifiers
DOI: 10.1111/j.1365-2443.2008.01208.x
PMID: 18651850
Source
Medline
License
Unknown

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.

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