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KSHV vCyclin Counters the Senescence/G1 Arrest Response Triggered by NF-κB Hyper-activation
Many oncogenic viruses activate NF-κB as a part of their replicative cycles. We have shown recently that persistent and potentially oncogenic activation of NF-κB by the human T-lymphotropic virus 1 (HTLV-1) oncoprotein Tax immediately triggers a host senescence response mediated by cyclin-dependent...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112183/ https://www.ncbi.nlm.nih.gov/pubmed/24469036 http://dx.doi.org/10.1038/onc.2013.567 |
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author | Zhi, Huijun Zahoor, Muhammad Atif Druck Shudofsky, Abigail M. Giam, Chou-Zen |
author_facet | Zhi, Huijun Zahoor, Muhammad Atif Druck Shudofsky, Abigail M. Giam, Chou-Zen |
author_sort | Zhi, Huijun |
collection | PubMed |
description | Many oncogenic viruses activate NF-κB as a part of their replicative cycles. We have shown recently that persistent and potentially oncogenic activation of NF-κB by the human T-lymphotropic virus 1 (HTLV-1) oncoprotein Tax immediately triggers a host senescence response mediated by cyclin-dependent kinase inhibitors: p21(CIP1/WAF1) (p21) and p27(Kip1) (p27) Here we demonstrate that RelA/NF-κB activation by Kaposi sarcoma herpesvirus (KSHV) latency protein vFLIP also leads to p21/p27 up-regulation and G1 cell cycle arrest. Remarkably, KSHV vCyclin, another latency protein co-expressed with vFLIP from a bicistronic latency-specific mRNA, was found to prevent the senescence and G1 arrest induced by HTLV-1 Tax and vFLIP respectively. This is due to the known ability of vCyclin/CDK6 complex to resist p21 and p27 inhibition and cause p27 degradation(23). In KSHV-transformed BCBL-1 cells, sustained vFLIP expression with shRNA-mediated vCyclin depletion resulted in G1 arrest. The functional interdependence of vFLIP and vCyclin explains why they are co-translated from the same viral mRNA. Importantly, deregulation of the G1 cyclin-dependent kinase can facilitate chronic IKK/NF-κB activation. |
format | Online Article Text |
id | pubmed-4112183 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
spelling | pubmed-41121832015-07-22 KSHV vCyclin Counters the Senescence/G1 Arrest Response Triggered by NF-κB Hyper-activation Zhi, Huijun Zahoor, Muhammad Atif Druck Shudofsky, Abigail M. Giam, Chou-Zen Oncogene Article Many oncogenic viruses activate NF-κB as a part of their replicative cycles. We have shown recently that persistent and potentially oncogenic activation of NF-κB by the human T-lymphotropic virus 1 (HTLV-1) oncoprotein Tax immediately triggers a host senescence response mediated by cyclin-dependent kinase inhibitors: p21(CIP1/WAF1) (p21) and p27(Kip1) (p27) Here we demonstrate that RelA/NF-κB activation by Kaposi sarcoma herpesvirus (KSHV) latency protein vFLIP also leads to p21/p27 up-regulation and G1 cell cycle arrest. Remarkably, KSHV vCyclin, another latency protein co-expressed with vFLIP from a bicistronic latency-specific mRNA, was found to prevent the senescence and G1 arrest induced by HTLV-1 Tax and vFLIP respectively. This is due to the known ability of vCyclin/CDK6 complex to resist p21 and p27 inhibition and cause p27 degradation(23). In KSHV-transformed BCBL-1 cells, sustained vFLIP expression with shRNA-mediated vCyclin depletion resulted in G1 arrest. The functional interdependence of vFLIP and vCyclin explains why they are co-translated from the same viral mRNA. Importantly, deregulation of the G1 cyclin-dependent kinase can facilitate chronic IKK/NF-κB activation. 2014-01-27 2015-01-22 /pmc/articles/PMC4112183/ /pubmed/24469036 http://dx.doi.org/10.1038/onc.2013.567 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Zhi, Huijun Zahoor, Muhammad Atif Druck Shudofsky, Abigail M. Giam, Chou-Zen KSHV vCyclin Counters the Senescence/G1 Arrest Response Triggered by NF-κB Hyper-activation |
title | KSHV vCyclin Counters the Senescence/G1 Arrest Response Triggered by NF-κB Hyper-activation |
title_full | KSHV vCyclin Counters the Senescence/G1 Arrest Response Triggered by NF-κB Hyper-activation |
title_fullStr | KSHV vCyclin Counters the Senescence/G1 Arrest Response Triggered by NF-κB Hyper-activation |
title_full_unstemmed | KSHV vCyclin Counters the Senescence/G1 Arrest Response Triggered by NF-κB Hyper-activation |
title_short | KSHV vCyclin Counters the Senescence/G1 Arrest Response Triggered by NF-κB Hyper-activation |
title_sort | kshv vcyclin counters the senescence/g1 arrest response triggered by nf-κb hyper-activation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112183/ https://www.ncbi.nlm.nih.gov/pubmed/24469036 http://dx.doi.org/10.1038/onc.2013.567 |
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