title: Human mediator kinase subunit CDK11 plays a negative role in viral activator VP16-dependent transcriptional regulation.
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.
authors.affiliation: Laboratory of Gene Regulation, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Tsutsui
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Umemura
authors.forename: Aki
authors.initials: A
authors.lastname: Tanaka
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Mizuki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hirose
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ohkuma
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D056850:Cyclin-Dependent Kinase 8; D018844:Cyclin-Dependent Kinases / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D017405:Herpes Simplex Virus Protein Vmw65 / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data
chemical_list: D017405:Herpes Simplex Virus Protein Vmw65; C447612:CDK11a protein, human; C095686:CDK8 protein, human; D056850:Cyclin-Dependent Kinase 8; D018844:Cyclin-Dependent Kinases