PS1-018 . Human Cytomegalovirus induces redistribution of the interferon inducible protein IFI16 from nucleus to cytoplasm

ABSTRACT Protein ISGylation is unique among ubiquitin-like conjugation systems in that the expression and conjugation processes are induced by specific stimuli, mainly via the alpha/beta interferon signaling pathway. It has been suggested that protein ISGylation plays a special role in the immune response, because of its interferon-signal dependency and its appearance only in higher eukaryotic organisms. Here, we report the identification of an ISG15-conjugating enzyme, Ubc8. Like other components of the protein ISGylation system (ISG15, UBE1L, and UBP43), Ubc8 is an interferon-inducible protein. Ubc8 clearly mediates protein ISGylation in transfection assays. The reduction of Ubc8 expression by small interfering RNA causes a decrease in protein ISGylation in HeLa cells upon interferon treatment. Neither UbcH7/UbcM4, the closest homologue of Ubc8 among known ubiquitin E2s, nor the small ubiquitin-like modifier E2 Ubc9 supports protein ISGylation. These findings strongly suggest that Ubc8 is a major ISG15-conjugating enzyme responsible for protein ISGylation upon interferon stimulation. Furthermore, we established an assay system to detect ISGylated target proteins by cotransfection of ISG15, UBE1L, and Ubc8 together with a target protein to be analyzed. This method provides an easy and effective way to identify new targets for the ISGylation system and will facilitate related studies.

Download Full-text

Relevance of Interferon-Inducible Protein-16 Rather than Anti-Interferon-Inducible Protein-16 Autoantibodies as a Clinical and Pathogenic Biomarker in Primary Sjögren's Syndrome: Comment on the Article by Baer et al

Arthritis Care & Research ◽

10.1002/acr.22918 ◽

2017 ◽

Vol 69 (3) ◽

pp. 453-454

Author(s):

Alessia Alunno ◽

Elena Bartoloni ◽

Onelia Bistoni ◽

Roberto Gerli ◽

Valeria Caneparo ◽

...

Keyword(s):

Sjögren’S Syndrome ◽

Sjögren's Syndrome ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Primary Sjögren’S Syndrome ◽

Primary Sjogren’S Syndrome ◽

Primary Sjögren's Syndrome ◽

Inducible Protein ◽

Interferon Inducible Protein ◽

Sjögren‘S Syndrome

Download Full-text

Gamma Interferon-Inducible Protein 10 Induces HeLa Cell Apoptosis through a p53-Dependent Pathway Initiated by Suppression of Human Papillomavirus Type 18 E6 and E7 Expression

Molecular and Cellular Biology ◽

10.1128/mcb.25.14.6247-6258.2005 ◽

2005 ◽

Vol 25 (14) ◽

pp. 6247-6258 ◽

Cited By ~ 44

Author(s):

Huifang M. Zhang ◽

Ji Yuan ◽

Paul Cheung ◽

David Chau ◽

Brian W. Wong ◽

...

Keyword(s):

Human Papillomavirus ◽

Viral Replication ◽

Cell Apoptosis ◽

Gamma Interferon ◽

Apoptotic Pathway ◽

Altered Expression ◽

E6 And E7 ◽

Inducible Protein ◽

Interferon Inducible Protein

ABSTRACT Gamma interferon-inducible protein 10 (IP10) is a member of the CXC family of chemokines. By differential mRNA display, we have demonstrated the upregulation of IP10 in coxsackievirus B3 (CVB3)-infected mouse hearts. Functional characterization of the IP10 gene in IP10-transfected Tet-On HeLa cells has found that IP10 induced cell apoptosis and inhibited viral replication. In the characterization of the IP10-induced apoptotic pathway, we found that overexpression of IP10 upregulated p53 and resulted in altered expression of p53-responsive genes such as the p21Cip1, p27kip1, NF-κB, Bax, and PUMA genes and the mitochondrial translocation of Bax. However, transduction of the IP10 cells with adenovirus expressing dominant negative p53 not only ablated p53-triggered gene expression but also abolished IP10-induced apoptosis and restored CVB3 replication to the control levels. These data suggest a novel mechanism by which IP10 inhibits viral replication through the induction of host cell death via a p53-mediated apoptotic pathway. We also found that constantly high-level expression of p53 in these tumor cells is attributed to the IP10-induced suppression of human papillomavirus E6 and E7 oncogene expression. Taken together, these data reveal not only a previously unrecognized link between chemokine IP10 and p53 in antiviral defense but also a mechanism by which IP10 inhibits tumor cell growth.

Download Full-text

Delta-like 1 contributes to cell growth by increasing the interferon-inducible protein 16 expression in hepatocellular carcinoma

Liver International ◽

10.1111/j.1478-3231.2010.02214.x ◽

2010 ◽

Vol 30 (5) ◽

pp. 703-714 ◽

Cited By ~ 17

Author(s):

Feng Yu ◽

Xiangfang Hao ◽

Heng Zhao ◽

Chao Ge ◽

Ming Yao ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Growth ◽

Inducible Protein ◽

Interferon Inducible Protein

Download Full-text

Abstract WP265: Interferon-inducible Protein 10 Increases following Stroke

Stroke ◽

10.1161/str.44.suppl_1.awp265 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Hilary A Seifert ◽

Lisa A Collier ◽

Stanley A Benkovic ◽

Alison E Willing ◽

Keith R Pennypacker

Keyword(s):

Time Course ◽

Neutralizing Antibody ◽

Artery Occlusion ◽

T Helper ◽

Protein Levels ◽

Organ Systems ◽

Inducible Protein ◽

Cerebral Artery Occlusion ◽

The Brain ◽

Interferon Inducible Protein

Objective: The splenic response to injury furthers cellular degeneration as its removal is protective in ischemic injuries to several organ systems including the brain. Previously, we have shown that the proinflammatory cytokine interferon gamma (IFNg), which activates microglia/macrophages, is elevated in the spleen and the brain following permanent middle cerebral artery occlusion (MCAO). IFNg induces the production of interferon-inducible protein 10 (IP-10) which further propagates the inflammatory response. Therefore, we investigated the expression of IP-10 in the brain and spleen following ischemic stroke. Hypothesis: IFNg production in the brain and the spleen results in elevated levels of IP-10 in the same tissues post-MCAO. Methods: A time course was conducted to investigate splenic and brain protein levels of IP-10 in rats over time following MCAO and sham-MCAO (n≥3). In a second experiment, rats were administered an IFNg neutralizing antibody following MCAO with a survival time of 96 h: vehicle control (n=4), goat IgG 5μg (n=7), and IFNg antibody 5μg (n=7). Spleens and brains were collected for all groups. Results: IP-10 levels were significantly elevated in the brain at 72 and 96 h post-MCAO (p<0.01) compared to naïve brains. In the spleen IP-10 levels become significantly elevated at 24 h and remain elevated out to 96 h post-MCAO (p<0.0007) compared to naïve spleens. Administration of a neutralizing antibody directed against IFNg significantly decreased IP-10 levels in the brain (p<0.009) but did not affect IP-10 levels in the spleen. Conclusion: These results demonstrate that increased production of IFNg results in elevated levels of IP-10 in both the spleen and the brain following stroke. However, administration of a neutralizing antibody against IFNg decreased the amount of IP-10 in the brain. Levels of IFNg and IP-10 in the brain increase at the same time following stroke. Based on these data, IFNg propagates a proinflammatory T helper cell response to stroke through IP-10. Inhibition of this signaling could reduce neuroinflammation thereby improving stroke outcome.

Download Full-text