Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhi, Huijun, Zahoor, Muhammad Atif, Druck Shudofsky, Abigail M., Giam, Chou-Zen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
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
_version_ 1782328157809934336
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
work_keys_str_mv AT zhihuijun kshvvcyclincountersthesenescenceg1arrestresponsetriggeredbynfkbhyperactivation
AT zahoormuhammadatif kshvvcyclincountersthesenescenceg1arrestresponsetriggeredbynfkbhyperactivation
AT druckshudofskyabigailm kshvvcyclincountersthesenescenceg1arrestresponsetriggeredbynfkbhyperactivation
AT giamchouzen kshvvcyclincountersthesenescenceg1arrestresponsetriggeredbynfkbhyperactivation