The retroviral cyclin of walleye dermal sarcoma virus binds cyclin-dependent kinases 3 and 8.
Walleye dermal sarcoma virus encodes a retroviral cyclin (rv-cyclin) with a cyclin box fold and transcription activation domain (AD). Co-immune precipitation (co-IP) identified an association of rv-cyclin with cyclin-dependent kinase 8 (cdk8). Cdk8 is dependent upon cyclin C and regulates transcription with the Mediator complex, a co-activator of transcription. Mutation of cyclin residues, required for cdk binding, disrupts rv-cyclin-cdk8 co-IP. Mutation or removal of the AD has no effect on cdk8 interaction. Direct rv-cyclin-cdk8 binding is demonstrated by pulldown of active cdk8 and by GST-rv-cyclin binding to recombinant cdk8. Cdk3 is also activated by cyclin C and phosphorylates retinoblastoma protein to initiate entry into the cell division cycle. Co-IP and pulldowns demonstrate direct rv-cyclin binding to cdk3 as well. The rv-cyclin functions as a structural ortholog of cyclin C in spite of its limited amino acid sequence identity with C cyclins or with any known cyclins.
Department of Microbiology, Immunology, and Pathology, 1619 Campus Delivery, Colorado State University, Fort Collins, CO 80523, USA. connie.brewster@colostate.edu
Connie D
CD
Brewster
Claire H
CH
Birkenheuer
Megan B
MB
Vogt
Sandra L
SL
Quackenbush
Joel
J
Rovnak
D056849:Cyclin-Dependent Kinase 3 / Q000378:metabolism*; D056850:Cyclin-Dependent Kinase 8 / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D030283:Epsilonretrovirus / Q000502:physiology*; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D047468:Immunoprecipitation; D011485:Protein Binding; D014764:Viral Proteins / Q000378:metabolism*
D016213:Cyclins; D014764:Viral Proteins; D056849:Cyclin-Dependent Kinase 3; D056850:Cyclin-Dependent Kinase 8