The Interactive Complex between Cytomegalovirus Kinase vCDK/pUL97 and Host Factors CDK7-Cyclin H Determines Individual Patterns of Transcription in Infected Cells
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
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| Enthalten in: |
International journal of molecular sciences - 24(2023), 24 vom: 13. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Schütz, Martin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.12.2023 Date Revised 25.12.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/ijms242417421 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM366299166 |
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| 100 | 1 | |a Schütz, Martin |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The Interactive Complex between Cytomegalovirus Kinase vCDK/pUL97 and Host Factors CDK7-Cyclin H Determines Individual Patterns of Transcription in Infected Cells |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a cyclin-dependent kinases (CDKs) | |
| 650 | 4 | |a first vCDK/pUL97-specific transcriptomic analysis | |
| 650 | 4 | |a functional complexation with host CDK7 | |
| 650 | 4 | |a human cytomegalovirus | |
| 650 | 4 | |a impact on RNA polymerase (RNAP II) in infected cells | |
| 650 | 4 | |a vCDK/pUL97–cyclin binding | |
| 650 | 4 | |a viral CDK ortholog (vCDK/pUL97) | |
| 650 | 7 | |a Cyclins |2 NLM | |
| 650 | 7 | |a Cyclin H |2 NLM | |
| 650 | 7 | |a Cyclin-Dependent Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.22 |2 NLM | |
| 700 | 1 | |a Cordsmeier, Arne |e verfasserin |4 aut | |
| 700 | 1 | |a Wangen, Christina |e verfasserin |4 aut | |
| 700 | 1 | |a Horn, Anselm H C |e verfasserin |4 aut | |
| 700 | 1 | |a Wyler, Emanuel |e verfasserin |4 aut | |
| 700 | 1 | |a Ensser, Armin |e verfasserin |4 aut | |
| 700 | 1 | |a Sticht, Heinrich |e verfasserin |4 aut | |
| 700 | 1 | |a Marschall, Manfred |e verfasserin |4 aut | |
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