Keywords : RV
European Journal of Molecular & Clinical Medicine,
2015, Volume 2, Issue 4, Pages -
Walleye dermal sarcoma virus is a complex retrovirus that causes seasonal tumors in walleye fish. RV-cyclin is one accessory protein encoded by the virus, and is one of only two viral proteins expressed during tumor development. Therefore, role of RV-cyclin in tumor development was explored. RV-cyclin interacts with host cyclin dependent kinase8 (CDK8). CDK8 has oncogenic like properties in colon cancer and melanoma, and one target of CDK8 kinase activity is the carboxy terminal domain of RNA Pol II. Here qRT-PCR analysis demonstrates RV-cyclins direct interaction with CDK8 increases transcript levels of another set of oncogenesthe serum-response genes (Fos, EGR1, and Jun). Nuclear run-on experiments, and chromatin immunoprecipitation experiments with an antibody to RNA Pol II, show that RV-cyclin enhances transcription elongation along the EGR1 gene locus. This enhancement correlates with increased recruitment of CDK8 to the EGR1 gene locus. In addition to increasing CDK8 occupancy at the EGR1 gene, in vitro kinase experiments demonstrate RV-cyclin increases the amount of CDK8-phosphorylation on the CTD of RNA Pol II. In conclusion, not only does RV-cyclin direct CDK8 to specific genes during tumor development, RV-cyclin enhances CDK8 kinase activity while it is there. The end result of the CDK8-RV-cyclin interaction is a rise in the mRNA levels of another pool of oncogenes, the serum-response genes. This is one mechanism by which RV-cyclin could contribute to the development of walleye dermal sarcoma.