CDK9 and SPT5 proteins are specifically required for expression of herpes simplex virus 1 replication-dependent late genes
© 2017 by The American Society for Biochemistry and Molecular Biology, Inc..
DNA replication greatly enhances expression of the herpes simplex virus 1 (HSV-1) γ2 late genes by still unknown mechanisms. Here, we demonstrate that 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole (DRB), an inhibitor of CDK9, suppresses expression of γ2 late genes with an IC50 of 5 μm, which is at least 10 times lower than the IC50 value required for inhibition of expression of early genes. The effect of DRB could not be explained by inhibition of DNA replication per se or loading of RNA polymerase II to late promoters and subsequent reduction of transcription. Instead, DRB reduces accumulation of γ2 late mRNA in the cytoplasm. In addition, we show that siRNA-mediated knockdown of the transcription factor SPT5, but not NELF-E, also gives rise to a specific inhibition of HSV-1 late gene expression. Finally, addition of DRB reduces co-immunoprecipitation of ICP27 using an anti-SPT5 antibody. Our results suggest that efficient expression of replication-dependent γ2 late genes is, at least in part, regulated by CDK9 dependent co- and/or post-transcriptional events involving SPT5 and ICP27.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2017 |
|---|---|
| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:292 |
|---|---|
| Enthalten in: |
The Journal of biological chemistry - 292(2017), 37 vom: 15. Sept., Seite 15489-15500 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Zhao, Zhiyuan [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 27.09.2017 Date Revised 05.02.2021 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1074/jbc.M117.806000 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM274184567 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM274184567 | ||
| 003 | DE-627 | ||
| 005 | 20231225002919.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2017 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1074/jbc.M117.806000 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0913.xml |
| 035 | |a (DE-627)NLM274184567 | ||
| 035 | |a (NLM)28743741 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Zhao, Zhiyuan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a CDK9 and SPT5 proteins are specifically required for expression of herpes simplex virus 1 replication-dependent late genes |
| 264 | 1 | |c 2017 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 27.09.2017 | ||
| 500 | |a Date Revised 05.02.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2017 by The American Society for Biochemistry and Molecular Biology, Inc. | ||
| 520 | |a DNA replication greatly enhances expression of the herpes simplex virus 1 (HSV-1) γ2 late genes by still unknown mechanisms. Here, we demonstrate that 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole (DRB), an inhibitor of CDK9, suppresses expression of γ2 late genes with an IC50 of 5 μm, which is at least 10 times lower than the IC50 value required for inhibition of expression of early genes. The effect of DRB could not be explained by inhibition of DNA replication per se or loading of RNA polymerase II to late promoters and subsequent reduction of transcription. Instead, DRB reduces accumulation of γ2 late mRNA in the cytoplasm. In addition, we show that siRNA-mediated knockdown of the transcription factor SPT5, but not NELF-E, also gives rise to a specific inhibition of HSV-1 late gene expression. Finally, addition of DRB reduces co-immunoprecipitation of ICP27 using an anti-SPT5 antibody. Our results suggest that efficient expression of replication-dependent γ2 late genes is, at least in part, regulated by CDK9 dependent co- and/or post-transcriptional events involving SPT5 and ICP27 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a cyclin-dependent kinase (CDK) | |
| 650 | 4 | |a gene expression | |
| 650 | 4 | |a herpesvirus | |
| 650 | 4 | |a post-transcriptional regulation | |
| 650 | 4 | |a viral replication | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Chromosomal Proteins, Non-Histone |2 NLM | |
| 650 | 7 | |a ICP27 protein, human herpesvirus 1 |2 NLM | |
| 650 | 7 | |a Immediate-Early Proteins |2 NLM | |
| 650 | 7 | |a Nucleic Acid Synthesis Inhibitors |2 NLM | |
| 650 | 7 | |a Protein Kinase Inhibitors |2 NLM | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
| 650 | 7 | |a Transcriptional Elongation Factors |2 NLM | |
| 650 | 7 | |a Viral Proteins |2 NLM | |
| 650 | 7 | |a negative elongation factor |2 NLM | |
| 650 | 7 | |a SPT5 transcriptional elongation factor |2 NLM | |
| 650 | 7 | |a 138673-72-0 |2 NLM | |
| 650 | 7 | |a Dichlororibofuranosylbenzimidazole |2 NLM | |
| 650 | 7 | |a 53-85-0 |2 NLM | |
| 650 | 7 | |a Cyclin-Dependent Kinase 9 |2 NLM | |
| 650 | 7 | |a EC 2.7.11.22 |2 NLM | |
| 700 | 1 | |a Tang, Ka-Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Muylaert, Isabella |e verfasserin |4 aut | |
| 700 | 1 | |a Samuelsson, Tore |e verfasserin |4 aut | |
| 700 | 1 | |a Elias, Per |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The Journal of biological chemistry |d 1945 |g 292(2017), 37 vom: 15. Sept., Seite 15489-15500 |w (DE-627)NLM000004995 |x 1083-351X |7 nnns |
| 773 | 1 | 8 | |g volume:292 |g year:2017 |g number:37 |g day:15 |g month:09 |g pages:15489-15500 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1074/jbc.M117.806000 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 292 |j 2017 |e 37 |b 15 |c 09 |h 15489-15500 | ||