The DRY box and C-terminal domain of the human cytomegalovirus US27 gene product play a role in promoting cell growth and survival.
Human cytomegalovirus (HCMV) is a widespread pathogen that can lay dormant in healthy individuals and establish lifelong latent infection. This successful co-existence is facilitated by a number of viral gene products that manipulate host cellular functions and immune responses. Among these immunomo...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4237426?pdf=render |
| _version_ | 1818024596771700736 |
|---|---|
| author | Carolyn C Tu Juliet V Spencer |
| author_facet | Carolyn C Tu Juliet V Spencer |
| author_sort | Carolyn C Tu |
| collection | DOAJ |
| description | Human cytomegalovirus (HCMV) is a widespread pathogen that can lay dormant in healthy individuals and establish lifelong latent infection. This successful co-existence is facilitated by a number of viral gene products that manipulate host cellular functions and immune responses. Among these immunomodulatory genes are four G-protein coupled receptors (GPCRs) encoded by HCMV, designated US27, US28, UL33, and UL78. Studies have shown the US28 gene product to be a functional chemokine receptor that signals both constitutively and in a ligand-dependent manner, resulting in a wide range of cellular effects. In previous work, we have found that US27 expression results in at least two biological effects: enhanced CXCR4 signaling and increased in cellular proliferation in HEK293 cells. Here, we examined the involvement of two protein domains, the DRY box and the C-terminal intracellular domain (CTD) of US27, in mediating both cell proliferation and survival. While both domains were required for a proliferative effect, loss of either domain only moderately impacted cell survival, suggesting that US27 may interact with cell survival pathways through protein regions other than the DRY box and CTD. Quantitative RT-PCR arrays were used to profile changes in cellular gene expression in the HEK293-US27 cell line, and down-regulation of cell cycle regulators CDKN1A/p21/CIP1 (cyclin dependent kinase inhibitor 1A) and SESN (Sestrin2 or Hi95) was observed. These results indicate that increased cell proliferation due to US27 may be linked to suppression of negative growth regulators, and that these interactions require the DRY box and CTD. |
| first_indexed | 2024-12-10T04:02:44Z |
| format | Article |
| id | doaj.art-9eb8f50d17e344b6953d92356b7ebab2 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T04:02:44Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9eb8f50d17e344b6953d92356b7ebab22022-12-22T02:02:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01911e11342710.1371/journal.pone.0113427The DRY box and C-terminal domain of the human cytomegalovirus US27 gene product play a role in promoting cell growth and survival.Carolyn C TuJuliet V SpencerHuman cytomegalovirus (HCMV) is a widespread pathogen that can lay dormant in healthy individuals and establish lifelong latent infection. This successful co-existence is facilitated by a number of viral gene products that manipulate host cellular functions and immune responses. Among these immunomodulatory genes are four G-protein coupled receptors (GPCRs) encoded by HCMV, designated US27, US28, UL33, and UL78. Studies have shown the US28 gene product to be a functional chemokine receptor that signals both constitutively and in a ligand-dependent manner, resulting in a wide range of cellular effects. In previous work, we have found that US27 expression results in at least two biological effects: enhanced CXCR4 signaling and increased in cellular proliferation in HEK293 cells. Here, we examined the involvement of two protein domains, the DRY box and the C-terminal intracellular domain (CTD) of US27, in mediating both cell proliferation and survival. While both domains were required for a proliferative effect, loss of either domain only moderately impacted cell survival, suggesting that US27 may interact with cell survival pathways through protein regions other than the DRY box and CTD. Quantitative RT-PCR arrays were used to profile changes in cellular gene expression in the HEK293-US27 cell line, and down-regulation of cell cycle regulators CDKN1A/p21/CIP1 (cyclin dependent kinase inhibitor 1A) and SESN (Sestrin2 or Hi95) was observed. These results indicate that increased cell proliferation due to US27 may be linked to suppression of negative growth regulators, and that these interactions require the DRY box and CTD.http://europepmc.org/articles/PMC4237426?pdf=render |
| spellingShingle | Carolyn C Tu Juliet V Spencer The DRY box and C-terminal domain of the human cytomegalovirus US27 gene product play a role in promoting cell growth and survival. PLoS ONE |
| title | The DRY box and C-terminal domain of the human cytomegalovirus US27 gene product play a role in promoting cell growth and survival. |
| title_full | The DRY box and C-terminal domain of the human cytomegalovirus US27 gene product play a role in promoting cell growth and survival. |
| title_fullStr | The DRY box and C-terminal domain of the human cytomegalovirus US27 gene product play a role in promoting cell growth and survival. |
| title_full_unstemmed | The DRY box and C-terminal domain of the human cytomegalovirus US27 gene product play a role in promoting cell growth and survival. |
| title_short | The DRY box and C-terminal domain of the human cytomegalovirus US27 gene product play a role in promoting cell growth and survival. |
| title_sort | dry box and c terminal domain of the human cytomegalovirus us27 gene product play a role in promoting cell growth and survival |
| url | http://europepmc.org/articles/PMC4237426?pdf=render |
| work_keys_str_mv | AT carolynctu thedryboxandcterminaldomainofthehumancytomegalovirusus27geneproductplayaroleinpromotingcellgrowthandsurvival AT julietvspencer thedryboxandcterminaldomainofthehumancytomegalovirusus27geneproductplayaroleinpromotingcellgrowthandsurvival AT carolynctu dryboxandcterminaldomainofthehumancytomegalovirusus27geneproductplayaroleinpromotingcellgrowthandsurvival AT julietvspencer dryboxandcterminaldomainofthehumancytomegalovirusus27geneproductplayaroleinpromotingcellgrowthandsurvival |