Stabilization of p53 in Influenza A Virus-infected Cells Is Associated with Compromised MDM2-mediated Ubiquitination of p53

Wang, Xiaodu; Deng, Xunming; Yan, Wenjun; Zhu, Zixiang; Shen, Yang; Qiu, Yafeng; Shi, Zhu‐Pei; Shao, Donghua; Wei, Jianchao; Xia, Xianzhu; Ma, Zhiyong

doi:10.1074/jbc.m111.335422

Cited by 45 publications

(45 citation statements)

References 34 publications

(43 reference statements)

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“…By targeting p53, viruses can control an important innate immune response, namely, apoptosis, for their own advantage. There are reports of virus-induced downregulation of p53 by degradation (10)(11)(12), inactivation of p53 transactivation (13,14), as well as stabilization of p53 (15)(16)(17), depending on the virus type or stage of viral replication.…”

mentioning

confidence: 99%

Rotavirus-Encoded Nonstructural Protein 1 Modulates Cellular Apoptotic Machinery by Targeting Tumor Suppressor Protein p53

Bhowmick

Halder

Chattopadhyay

et al. 2013

J Virol

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b p53, a member of the innate immune system, is triggered under stress to induce cell growth arrest and apoptosis. Thus, p53 is an important target for viruses, as efficient infection depends on modulation of the host apoptotic machinery. This study focuses on how rotaviruses manipulate intricate p53 signaling for their advantage. Analysis of p53 expression revealed degradation of p53 during initial stages of rotavirus infection. However, in nonstructural protein-1 (NSP1) mutant strain A5-16, p53 degradation was not observed, suggesting a role of NSP1 in this process. This function of NSP1 was independent of its interferon or phosphatidylinositol 3-kinase (PI3K)/AKT modulation activity since p53 degradation was observed in Vero cells as well as in the presence of PI3K inhibitor. p53 transcript levels remained the same in SA11-infected cells (at 2 to 14 h postinfection), but p53 protein was stabilized only in the presence of MG132, suggesting a posttranslational process. NSP1 interacted with the DNA binding domain of p53, resulting in ubiquitination and proteasomal degradation of p53. Degradation of p53 during initial stages of infection inhibited apoptosis, as the proapoptotic genes PUMA and Bax were downregulated. During late viral infection, when progeny dissemination is the main objective, the NSP1-p53 interaction was diminished, resulting in restoration of the p53 level, with initiation of proapoptotic signaling ensuing. Overall results highlight the multiple strategies evolved by NSP1 to combat the host immune response.

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confidence: 99%

Rotavirus-Encoded Nonstructural Protein 1 Modulates Cellular Apoptotic Machinery by Targeting Tumor Suppressor Protein p53

Bhowmick

Halder

Chattopadhyay

et al. 2013

J Virol

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“…All cells were cultured in their medium supplemented with 10% fetal bovine serum at 37°C under 5% CO 2 . Viral infection was as described previously [27]. All animal experiments were performed in compliance with the Guidelines on the Humane Treatment of Laboratory Animals (Ministry of Science and Technology of the People's Republic of China, Policy No.…”

Section: Methodsmentioning

confidence: 99%

“…Construction of expression plasmids for BiFC assay was performed as previously described [27]. Sequences encoding the N-(amino acids 1–173) and C- (amino acids 174–239) terminal fragments of VFP were fused by a short linker to hGBP1 (hGBP1-VN) and NS1 gene (NS1-VC), respectively.…”

Section: Supporting Informationmentioning

confidence: 99%

Nonstructural Protein 1 of Influenza A Virus Interacts with Human Guanylate-Binding Protein 1 to Antagonize Antiviral Activity

et al. 2013

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Human guanylate-binding protein 1 (hGBP1) is an interferon-inducible protein involved in the host immune response against viral infection. In response to infection by influenza A virus (IAV), hGBP1 transcript and protein were significantly upregulated. Overexpression of hGBP1 inhibited IAV replication in a dose-dependent manner in vitro. The lysine residue at position 51 (K51) of hGBP1 was essential for inhibition of IAV replication. Mutation of K51 resulted in an hGBP1 that was unable to inhibit IAV replication. The viral nonstructural protein 1 (NS1) was found to interact directly with hGBP1. K51 of hGBP1 and a region between residues 123 and 144 in NS1 were demonstrated to be essential for the interaction between NS1 and hGBP1. Binding of NS1 to hGBP1 resulted in a significant reduction in both GTPase activity and the anti-IAV activity of hGBP1. These findings indicated that hGBP1 contributed to the host immune response against IAV replication and that hGBP1-mediated antiviral activity was antagonized by NS1 via binding to hGBP1.

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“…The cycloheximide (CHX) was used to block protein synthesis of cells and evaluate the half-life of PKR protein. The PK-15 cells were cultured in the presence or absence of 100 μg/mL of CHX for the indicated periods at 37°C (Wang et al, 2012b). The collected cells were subjected to western blotting analysis.…”

Section: Chemical Inhibitors Assaymentioning

confidence: 99%

Foot-and-mouth disease virus induces lysosomal degradation of host protein kinase PKR by 3C proteinase to facilitate virus replication

Zhu

et al. 2017

Virology

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The interferon-induced double-strand RNA activated protein kinase (PKR) plays important roles in host defense against viral infection. Here we demonstrate the significant antiviral role of PKR against foot-and-mouth disease virus (FMDV) and report that FMDV infection inhibits PKR expression and activation in porcine kidney (PK-15) cells. The viral nonstructural protein 3C proteinase (3C) is identified to be responsible for this inhibition. However, it is independent of the well-known proteinase activity of 3C or 3C-induced shutoff of host protein synthesis. We show that 3C induces PKR degradation by lysosomal pathway and no interaction is determined between 3C and PKR. Together, our results indicate that PKR acts an important antiviral factor during FMDV infection, and FMDV has evolved a strategy to overcome PKR-mediated antiviral role by downregulation of PKR protein.

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Stabilization of p53 in Influenza A Virus-infected Cells Is Associated with Compromised MDM2-mediated Ubiquitination of p53

Cited by 45 publications

References 34 publications

Rotavirus-Encoded Nonstructural Protein 1 Modulates Cellular Apoptotic Machinery by Targeting Tumor Suppressor Protein p53

Rotavirus-Encoded Nonstructural Protein 1 Modulates Cellular Apoptotic Machinery by Targeting Tumor Suppressor Protein p53

Nonstructural Protein 1 of Influenza A Virus Interacts with Human Guanylate-Binding Protein 1 to Antagonize Antiviral Activity

Foot-and-mouth disease virus induces lysosomal degradation of host protein kinase PKR by 3C proteinase to facilitate virus replication

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