The constitutive activity of the viral-encoded G protein-coupled receptor US28 supports a complex signalling network contributing to cancer development

Carole A. Daly; Martine J. Smit; Bianca Plouffe

doi:10.1042/BST20190988

The constitutive activity of the viral-encoded G protein-coupled receptor US28 supports a complex signalling network contributing to cancer development

Carole A. Daly, Martine J. Smit, Bianca Plouffe

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

US28 is a viral G protein-coupled receptor (GPCR) encoded by the human cytomegalovirus (HCMV). This receptor, expressed both during lytic replication and viral latency, is required for latency. US28 is binding to a wide variety of chemokines but also exhibits a particularly high constitutive activity robustly modulating a wide network of cellular pathways altering the host cell environment to benefit HCMV infection. Several studies suggest that US28-mediated signalling may contribute to cancer progression. In this review, we discuss the unique structural characteristics that US28 acquired through evolution that confer a robust constitutive activity to this viral receptor. We also describe the wide downstream signalling network activated by this constitutive activation of US28 and discuss how these signalling pathways may promote and support important cellular aspects of cancer.

Original language	English
Pages (from-to)	1493-1504
Number of pages	12
Journal	Biochemical Society transactions
Volume	48
Issue number	4
DOIs	https://doi.org/10.1042/BST20190988
Publication status	Published - 28 Aug 2020

Funding

C.A.D. is supported by a PhD scholarship from the Department for Education (DfE) from Queen’s University Belfast. M.J.S. is supported by the Dutch Research Council (NWO—Vici 016.140.657). B.P. is funded by a Patrick G. Johnston/Vice-Chancellor’s Fellowship from Queen’s University Belfast and a Wellcome Trust Seed Award in Science (215229/Z/19/Z). C.A.D. is supported by a PhD scholarship from the Department for Education (DfE) from Queen?s University Belfast. M.J.S. is supported by the Dutch Research Council (NWO?Vici 016.140.657). B.P. is funded by a Patrick G. Johnston/Vice-Chancellor?s Fellowship from Queen?s University Belfast and a Wellcome Trust Seed Award in Science (215229/Z/19/Z).

Funders	Funder number
Department for Education
Dutch Research Council
Queen’s University Belfast
Wellcome Trust	215229/Z/19/Z
Queen's University Belfast
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	016.140.657

Keywords

cancer
chemokine receptor
constitutive activity
signalling network
US28
viral GCPR

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1042/BST20190988

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abstract = "US28 is a viral G protein-coupled receptor (GPCR) encoded by the human cytomegalovirus (HCMV). This receptor, expressed both during lytic replication and viral latency, is required for latency. US28 is binding to a wide variety of chemokines but also exhibits a particularly high constitutive activity robustly modulating a wide network of cellular pathways altering the host cell environment to benefit HCMV infection. Several studies suggest that US28-mediated signalling may contribute to cancer progression. In this review, we discuss the unique structural characteristics that US28 acquired through evolution that confer a robust constitutive activity to this viral receptor. We also describe the wide downstream signalling network activated by this constitutive activation of US28 and discuss how these signalling pathways may promote and support important cellular aspects of cancer.",

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AB - US28 is a viral G protein-coupled receptor (GPCR) encoded by the human cytomegalovirus (HCMV). This receptor, expressed both during lytic replication and viral latency, is required for latency. US28 is binding to a wide variety of chemokines but also exhibits a particularly high constitutive activity robustly modulating a wide network of cellular pathways altering the host cell environment to benefit HCMV infection. Several studies suggest that US28-mediated signalling may contribute to cancer progression. In this review, we discuss the unique structural characteristics that US28 acquired through evolution that confer a robust constitutive activity to this viral receptor. We also describe the wide downstream signalling network activated by this constitutive activation of US28 and discuss how these signalling pathways may promote and support important cellular aspects of cancer.

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The constitutive activity of the viral-encoded G protein-coupled receptor US28 supports a complex signalling network contributing to cancer development

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UN SDGs

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