Influenza NS1 interacts with p53 and alters its binding to p53‐responsive genes, in a promoter‐dependent manner

Terrier, B.; Diederichs, Audrey; Dubois, Julia; Cartet, Gaëlle; Lina, Bruno; Bourdon, Jean-Christophe; Rosa‐Calatrava, Manuel

doi:10.1016/j.febslet.2013.08.006

Cited by 19 publications

(24 citation statements)

References 22 publications

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“…NP impaired MDM2‐mediated p53 ubiquitination by associating with p53 to prevent interaction with MDM2 (Wang et al ., ). IVA non‐structural protein 1 (NS1) also enters the nucleolus (Melen et al ., 2007; 2012; Emmott et al ., ) and associates with p53 (Terrier et al ., ) but, in contrast to NP, inhibits p53‐mediated transcriptional activity and apoptosis (Wang et al ., ). Thus, it appears that IVA might mediate a complex‐regulatory interplay with the nucleolus/p53 to regulate apoptosis, possibly to inhibit antiviral apoptosis during early stages of infection, while inducing proapoptotic effects late in infection to facilitate viral spread.…”

Section: Viral Targeting Of the Nucleolusmentioning

confidence: 99%

“…NP impaired MDM2-mediated p53 ubiquitination by associating with p53 to prevent interaction with MDM2 . IVA non-structural protein 1 (NS1) also enters the nucleolus (Melen et al, 2007;Emmott et al, 2010a) and associates with p53 (Terrier et al, 2013) but, in contrast to NP, inhibits p53-mediated transcriptional activity and apoptosis (Wang et al, 2010b).…”

Section: Viral Control Of Nucleolar Function In Cellular Stress Respomentioning

confidence: 99%

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The nucleolar interface of RNA viruses

Rawlinson

Moseley

2015

Cell Microbiol

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SummaryIn recent years, understanding of the nucleolus has undergone a renaissance. Once considered primarily as the sites of ribosome biogenesis, nucleoli are now understood to be highly dynamic, multifunctional structures that participate in a plethora of cellular functions including regulation of the cell cycle, signal recognition particle assembly, apoptosis and stress responses. Although the molecular/mechanistic details of many of these functions remain only partially resolved, it is becoming increasingly apparent that nucleoli are also common targets of almost all types of viruses, potentially allowing viruses to manipulate cellular responses and the intracellular environment to facilitate replication and propagation. Importantly, a number of recent studies have moved beyond early descriptive observations to identify key roles for nucleolar interactions in the viral life cycle and pathogenesis. While it is perhaps unsurprising that many viruses that replicate within the nucleus also form interactions with nucleoli, the roles of nucleoli in the biology of cytoplasmic viruses is less intuitive. Nevertheless, a number of positivestranded RNA viruses that replicate exclusively in the cytoplasm are known to express proteins that enter the nucleus and target nucleoli, and recent data have indicated similar processes in several cytoplasmic negative-sense RNA viruses. Here, we review this emerging aspect of the virus-host interface with a focus on examples where virusnucleolus interactions have been linked to specific functional outcomes/mechanistic processes in infection and on the nucleolar interfaces formed by viruses that replicate exclusively in the cytoplasm.

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Section: Viral Targeting Of the Nucleolusmentioning

confidence: 99%

Section: Viral Control Of Nucleolar Function In Cellular Stress Respomentioning

confidence: 99%

The nucleolar interface of RNA viruses

Rawlinson

Moseley

2015

Cell Microbiol

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“…Indeed, we recently reported that p53 isoforms are also differentially regulated in response to flu virus infection and play an active role in regulating flu virus production 84,94–96…”

Section: Role Of P53 Isoforms In Human Cancer and Other Pathologiesmentioning

confidence: 99%

Uncovering the role of p53 splice variants in human malignancy: a clinical perspective

Surget¹,

Khoury²,

Bourdon³

2013

OTT

Self Cite

223

140

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Thirty-five years of research on p53 gave rise to more than 68,000 articles and reviews, but did not allow the uncovering of all the mysteries that this major tumor suppressor holds. How p53 handles the different signals to decide the appropriate cell fate in response to a stress and its implication in tumorigenesis and cancer progression remains unclear. Nevertheless, the uncovering of p53 isoforms has opened new perspectives in the cancer research field. Indeed, the human TP53 gene encodes not only one but at least twelve p53 protein isoforms, which are produced in normal tissues through alternative initiation of translation, usage of alternative promoters, and alternative splicing. In recent years, it became obvious that the different p53 isoforms play an important role in regulating cell fate in response to different stresses in normal cells by differentially regulating gene expression. In cancer cells, abnormal expression of p53 isoforms contributes actively to cancer formation and progression, regardless of TP53 mutation status. They can also be associated with response to treatment, depending on the cell context. The determination of p53 isoform expression and p53 mutation status helps to define different subtypes within a particular cancer type, which would have different responses to treatment. Thus, the understanding of the regulation of p53 isoform expression and their biological activities in relation to the cellular context would constitute an important step toward the improvement of the diagnostic, prognostic, and predictive values of p53 in cancer treatment. This review aims to summarize the involvement of p53 isoforms in cancer and to highlight novel potential therapeutic targets.

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“…Therefore, IAV has developed different strategies to regulate host‐cell P53‐dependent pathways to ensure the viral life cycle. For instance, viral‐NS1 can inhibit P53 transcriptional activity and to mediate cell survival during infection . Importantly, the rescue of P53 activity during viral infection has become an area of a therapeutic option to limit viral replication and distribution .…”

Section: Discussionmentioning

confidence: 99%

“…For instance, viral-NS1 can inhibit P53 transcriptional activity and to mediate cell survival during infection. 46 Importantly, the rescue of P53 activity during viral infection has become an area of a therapeutic option to limit viral replication and distribution. 47,48 While targeting Akt kinase and its connected signaling, mTOR and PI3K disturb IAV entry and inhibit viral replication.…”

Section: Discussionmentioning

confidence: 99%

Guava flavonoid glycosides prevent influenza A virus infection via rescue of P53 activity

Khalil

Maksoud

Roshdey

et al. 2018

Journal of Medical Virology

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Influenza is a highly infectious disease caused by three types of viruses, including influenza A virus (IAV), influenza B virus, and, rarely, influenza C virus. IAV is a major, global public health threat, causing approximately 500 000 deaths per year worldwide. The new strains of IAV have emerged due to a mutation called antigenic shift, which results in a new subtype of the virus that shows resistance to common antiviral drugs. Here, guava and lemon extracts, including green leaves and flowers, were investigated for their activity against IAV replication in human A549 cells. Concomitantly, the cytotoxicity of a potent extract on host-cell multiplication was assessed. Our results reveal that guava extracts inhibit IAV replication, indicated by viral nucleoprotein expression profile and traditional plaque assay. Interestingly, treatment with guava extract inactivates Akt protein kinase and stimulates the pro-apoptotic protein P53, at early stages of infection. Furthermore, purified guava flavonoid glycosides (GFGs) show competitive inhibition of IAV-virus replication via early regulation of IL-1β and IL-8 in association with P53 gene expression. The docking analysis of GFGs and the protein structure of upstream targets for the Akt signaling pathway indicates a sufficient interaction and stabilization with Gbr2 protein. These data indicate that treatment with GFGs disturbs IAV replication via activation of P53 and its apoptotic related factors after infection. Collectively, these data show that targeting of essential host kinases that are involved in the replication cycle of IAV and rescue of P53 activity by GFGs could represent a new strategy to eradicate IAV.

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Influenza NS1 interacts with p53 and alters its binding to p53‐responsive genes, in a promoter‐dependent manner

Cited by 19 publications

References 22 publications

The nucleolar interface of RNA viruses

The nucleolar interface of RNA viruses

Uncovering the role of p53 splice variants in human malignancy: a clinical perspective

Guava flavonoid glycosides prevent influenza A virus infection via rescue of P53 activity

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