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| Item Type: | Article |
|---|---|
| Title: | The interactive complex between cytomegalovirus kinase vCDK/pUL97 and host factors CDK7-cyclin H determines individual patterns of transcription in infected cells |
| Creators Name: | Schütz, M., Cordsmeier, A., Wangen, C., Horn, A.H.C., Wyler, E., Ensser, A., Sticht, H. and Marschall, M. |
| Abstract: | The infection of human cytomegalovirus (HCMV) is strongly determined by the host-cell interaction in a way that the efficiency of HCMV lytic replication is dependent on the regulatory interplay between viral and cellular proteins. In particular, the activities of protein kinases, such as cyclin-dependent kinases (CDKs) and the viral CDK ortholog (vCDK/pUL97), play an important role in both viral reproduction and virus-host interaction. Very recently, we reported on the complexes formed between vCDK/pUL97, human cyclin H, and CDK7. Major hallmarks of this interplay are the interaction between cyclin H and vCDK/pUL97, which is consistently detectable across various conditions and host cell types of infection, the decrease or increase in pUL97 kinase activity resulting from cyclin H knock-down or elevated levels, respectively, and significant trans-stimulation of human CDK7 activity by pUL97 in vitro. Due to the fact that even a ternary complex of vCDK/pUL97-cyclin H-CDK7 can be detected by coimmunoprecipitation and visualized by bioinformatic structural modeling, we postulated a putative impact of the respective kinase activities on the patterns of transcription in HCMV-infected cells. Here, we undertook a first vCDK/pUL97-specific transcriptomic analysis, which combined conditions of fully lytic HCMV replication with those under specific vCDK/pUL97 or CDK7 drug-mediated inhibition or transient cyclin H knockout. The novel results were further strengthened using bioinformatic modeling of the involved multi-protein complexes. Our data underline the importance of these kinase activities for the C-terminal domain (CTD) phosphorylation-driven activation of host RNA polymerase in HCMV-infected cells. The impact of the individual experimental conditions on differentially expressed gene profiles is described in detail and discussed. |
| Keywords: | Human Cytomegalovirus, Cyclin-Dependent Kinases (CDKs), Viral CDK Ortholog (vCDK/pUL97), vCDK/pUL97–Cyclin Binding, Functional Complexation with Host CDK7, Impact on RNA Polymerase (RNAP II) in Infected Cells, First vCDK/pUL97-Specific Transcriptomic Analysis |
| Source: | International Journal of Molecular Sciences |
| ISSN: | 1422-0067 |
| Publisher: | MDPI |
| Volume: | 24 |
| Number: | 24 |
| Page Range: | 17421 |
| Date: | 13 December 2023 |
| Official Publication: | https://doi.org/10.3390/ijms242417421 |
| PubMed: | View item in PubMed |
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