• Corpus ID: 73525402

p 53 controls hepatitis C virus non-structural protein 5 A-mediated downregulation of GADD 45 a expression via the NFk B and PI 3 K – Akt pathways

@inproceedings{Cheng2013p5C,
  title={p 53 controls hepatitis C virus non-structural protein 5 A-mediated downregulation of GADD 45 a expression via the NFk B and PI 3 K – Akt pathways},
  author={Du Cheng and Lei Zhao and Leiliang Zhang and Yongfang Jiang and Yi Tian and Xin-qiang Xiao and Guozhong Gong},
  year={2013}
}
Received 17 July 2012 Accepted 29 October 2012 Liver Diseases Center, Department of Infectious Diseases, Second Xiangya Hospital, Xiangya Medical School, Central South University, Changsha 410011, PR China Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical… 
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The Hepatitis C Virus NS5A Protein Activates a Phosphoinositide 3-Kinase-dependent Survival Signaling Cascade*

NS5A-mediated activation of PI3K resulted in increased phosphorylation and activity of Akt/protein kinase B and concomitantly provided protection against the induction of apoptosis in both replicon-harboring cells and cells stably expressing NS5A alone, suggesting potential therapeutic strategies to counteract the occurrence of HCV-related HCC.

Antiapoptotic and Oncogenic Potentials of Hepatitis C Virus Are Linked to Interferon Resistance by Viral Repression of the PKR Protein Kinase

Disruption of apoptosis and tumorogenesis required the PKR-binding function of NS5A, demonstrating that these properties may be linked to the IFN-resistant phenotype of HCV.

Human hepatitis C virus NS5A protein alters intracellular calcium levels, induces oxidative stress, and activates STAT-3 and NF-κB

An insight is provided into the mechanism by which NS5A can alter intracellular events relevant to liver pathogenesis associated with the viral infection.

Hepatitis C Virus Infection Induces Apoptosis through a Bax-Triggered, Mitochondrion-Mediated, Caspase 3-Dependent Pathway

It is suggested that HCV infection induces apoptosis of the host cell through a Bax-triggered, mitochondrion-mediated, caspase 3-dependent pathway(s), and that ER stress is not primarily involved in HCV-induced apoptosis in the authors' experimental system.

Activation of transcription factor Nrf2 by hepatitis C virus induces the cell-survival pathway.

An insight is provided into the mechanisms by which HCV induces intracellular events relevant to chronic HCV infection and a potential role for HCV-mediated Nrf2 activation in the survival ofHCV-infected cells, a condition favourable for liver oncogenesis.

HCV NS5A interacts with p53 and inhibits p53-mediated apoptosis

It is suggested that HCV NS5A interacts with and partially sequestrates p53 and hTAFII32 in the cytoplasm and suppresses p53-mediated transcriptional transactivation and apoptosis during HCV infection, which may contribute to the hepatocarcinogenesis ofHCV infection.

Hepatitis C virus NS5A protein modulates cell cycle regulatory genes and promotes cell growth.

Results suggested that NS5A protein represses transcription of the cell cycle regulatory gene p21WAF1, while it activates the human proliferating cell nuclear antigen gene in murine fibroblasts and human hepatoma cells.

Hepatitis C Virus NS5A-Mediated Activation of Phosphoinositide 3-Kinase Results in Stabilization of Cellular β-Catenin and Stimulation of β-Catenin-Responsive Transcription

Given the prevalence of β-catenin mutations in many human tumors, especially colon and hepatocellular carcinomas, these data implicate NS5A-mediated PI3K activation as a contributory factor in the increasingly common association between HCV infection and the development of hepatoma.

Activation of the N-Ras–PI3K–Akt-mTOR Pathway by Hepatitis C Virus: Control of Cell Survival and Viral Replication

Data suggest that increased N-Ras levels in subcellular sites of HCV replication and stimulation of the prosurvival PI3K-Akt pathway and mTOR by HCV not only protect cells against apoptosis but also contribute to the maintenance of steady-state levels ofHCV replication.

Hepatitis C Virus NS5A Physically Associates with p53 and Regulates p21/waf1 Gene Expression in a p53-Dependent Manner

Results suggest that an association of NS5A and p53 allows transcriptional modulation of the p21/waf1 gene and may contribute to HCV-mediated pathogenesis.