Mapping the Protein Phosphatase 1 Interactome in Human Cytomegalovirus Infection
Protein phosphorylation is a crucial regulatory mechanism in cellular homeostasis. The human cytomegalovirus (HCMV) incorporates protein phosphatase 1 (PP1) into its tegument, yet the biological relevance and mechanisms of this incorporation remain unclear. Our study offers the first characterizatio...
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MDPI AG
2024-12-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/16/12/1961 |
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| author | Stefan Weinberger Carmen Stecher Marie-Theres Kastner Sergei Nekhai Christoph Steininger |
| author_facet | Stefan Weinberger Carmen Stecher Marie-Theres Kastner Sergei Nekhai Christoph Steininger |
| author_sort | Stefan Weinberger |
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| description | Protein phosphorylation is a crucial regulatory mechanism in cellular homeostasis. The human cytomegalovirus (HCMV) incorporates protein phosphatase 1 (PP1) into its tegument, yet the biological relevance and mechanisms of this incorporation remain unclear. Our study offers the first characterization of the PP1 interactome during HCMV infection and its alterations. Using co-immunoprecipitation, mass spectrometry, and quantitative proteomics, we identified 159 high-confidence interacting proteins (HCIPs) in the PP1 interactome, consisting of 126 human and 33 viral proteins. We observed significant temporal changes in the PP1 interactome following HCMV infection, including the altered interactions of PP1 regulatory subunits. Further analysis highlighted the central roles of these PP1 interacting proteins in intracellular trafficking, with particular emphasis on the trafficking protein particle complex and Rab GTPases, which are crucial for the virus’s manipulation of host cellular processes in virion assembly and egress. Additionally, our study on the noncatalytic PP1 inhibitor 1E7-03 revealed a decrease in PP1’s interaction with key HCMV proteins, supporting its potential as an antiviral agent. Our findings suggest that PP1 docking motifs are critical in viral–host interactions and offer new insights for antiviral strategies. |
| format | Article |
| id | doaj-art-c4f658a8fc6d44cda7ab0d6bfb073150 |
| institution | Kabale University |
| issn | 1999-4915 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
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| series | Viruses |
| spelling | doaj-art-c4f658a8fc6d44cda7ab0d6bfb0731502024-12-27T14:59:22ZengMDPI AGViruses1999-49152024-12-011612196110.3390/v16121961Mapping the Protein Phosphatase 1 Interactome in Human Cytomegalovirus InfectionStefan Weinberger0Carmen Stecher1Marie-Theres Kastner2Sergei Nekhai3Christoph Steininger4Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, 1090 Vienna, AustriaDivision of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, 1090 Vienna, AustriaDivision of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, 1090 Vienna, AustriaCenter for Sickle Cell Disease, Howard University, Washington, DC 20059, USADivision of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, 1090 Vienna, AustriaProtein phosphorylation is a crucial regulatory mechanism in cellular homeostasis. The human cytomegalovirus (HCMV) incorporates protein phosphatase 1 (PP1) into its tegument, yet the biological relevance and mechanisms of this incorporation remain unclear. Our study offers the first characterization of the PP1 interactome during HCMV infection and its alterations. Using co-immunoprecipitation, mass spectrometry, and quantitative proteomics, we identified 159 high-confidence interacting proteins (HCIPs) in the PP1 interactome, consisting of 126 human and 33 viral proteins. We observed significant temporal changes in the PP1 interactome following HCMV infection, including the altered interactions of PP1 regulatory subunits. Further analysis highlighted the central roles of these PP1 interacting proteins in intracellular trafficking, with particular emphasis on the trafficking protein particle complex and Rab GTPases, which are crucial for the virus’s manipulation of host cellular processes in virion assembly and egress. Additionally, our study on the noncatalytic PP1 inhibitor 1E7-03 revealed a decrease in PP1’s interaction with key HCMV proteins, supporting its potential as an antiviral agent. Our findings suggest that PP1 docking motifs are critical in viral–host interactions and offer new insights for antiviral strategies.https://www.mdpi.com/1999-4915/16/12/1961cytomegalovirusprotein phosphatase 1interactomeproteomicsintracellular trafficking |
| spellingShingle | Stefan Weinberger Carmen Stecher Marie-Theres Kastner Sergei Nekhai Christoph Steininger Mapping the Protein Phosphatase 1 Interactome in Human Cytomegalovirus Infection Viruses cytomegalovirus protein phosphatase 1 interactome proteomics intracellular trafficking |
| title | Mapping the Protein Phosphatase 1 Interactome in Human Cytomegalovirus Infection |
| title_full | Mapping the Protein Phosphatase 1 Interactome in Human Cytomegalovirus Infection |
| title_fullStr | Mapping the Protein Phosphatase 1 Interactome in Human Cytomegalovirus Infection |
| title_full_unstemmed | Mapping the Protein Phosphatase 1 Interactome in Human Cytomegalovirus Infection |
| title_short | Mapping the Protein Phosphatase 1 Interactome in Human Cytomegalovirus Infection |
| title_sort | mapping the protein phosphatase 1 interactome in human cytomegalovirus infection |
| topic | cytomegalovirus protein phosphatase 1 interactome proteomics intracellular trafficking |
| url | https://www.mdpi.com/1999-4915/16/12/1961 |
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