Viral transactivators E1A and VP16 interact with a large complex that is associated with CTD kinase activity and contains CDK8

Article Article scientifique Article Viral transactivators E1A and VP16 interact with a large complex that is associated with CTD kinase activity and contains CDK8 eng 1996 author Gold Moses O. author Tassan Jean-Pierre author Nigg Erich A. 102131 author Rice Andrew P. author Herrmann Christine 80758 3771-3777 10.1093/nar/24.19.3771 0305-1048 https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/24.19.3771 Previously, we showed that the viral transactivator proteins E1A and VP16 specifically interact with a cellular CTD kinase activity in vitro . We now report that E1A and VP16 complexes contain human CDK8, a newly identified member of the cyclin-dependent kinase family that has been shown to be a component of the RNA polymerase II (RNAP II) holoenzyme complex. The presence of CDK8 in the E1A- and VP16-containing complexes is specific for a functional activation domain of these viral transactivators, strongly suggesting that this association is relevant for the transactivation function of E1A and VP16. We show that CDK8 is associated with CTD kinase activity and that CDK8 co-fractionates with E1A- and VP16-associated CTD kinase activity over several chromatography columns. Therefore, CDK8 is likely responsible for the E1A- and VP16-associated CTD kinase activity. Gel filtration chromatography indicates that the E1A- and VP16-associated CTD kinase activity has a molecular size of ∼1.5 MDa and contains cyclin C and the human homolog of SRB7 in addition to CDK8. This implies that E1A and VP16 associate with the RNAP II holoenyzme. We also looked at the transcriptional activity of CDK8 and found that CDK8 can function as a transcriptional activator when fused to the DNA binding domain of GAL4. Surprisingly, the ability of GAL4-CDK8 to activate transcription in this assay was not dependent on the kinase activity of CDK8, since a kinase-deficient mutant of CDK8 stimulated transcription nearly as well as wild-type GAL4-CDK8. This suggests that CDK8 may play a role in transcription that is distinct from its ability to function as a CTD kinase. Dewey 570 Swiss National Science Foundation 31-33615.92 CH 43 Département de biologie moléculaire 161 false Nucleic Acids Research 24 19 b06c8afb-cac2-4336-820e-87970dab4500 Article (Published version) Public 24-19-3771.pdf 87821 application/pdf CC BY openAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire

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Viral transactivators E1A and VP16 interact with a large complex that is associated with CTD kinase activity and contains CDK8	Nucleic Acids Research			1996	280	200

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Herrmann, Christine