Negative regulation of the retinoic acid-inducible gene I-induced antiviral state by the ubiquitin-editing protein A20.

Negative regulation of the retinoic acid-inducible gene I-induced antiviral state by the ubiquitin-editing protein A20. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Negative regulation of the retinoic acid-inducible gene I-induced antiviral state by the ubiquitin-editing protein A20. Abstract Text:

Rongtuan Lin,Long Yang,Peyman Nakhaei,Qiang Sun,Ehssan Sharif-Askari,Ilkka Julkunen,John Hiscott,

Activation of the interferon regulatory factors (IRFs) 3 and 7 transcription factors is essential for the induction of type I interferon (IFN) and development of the innate antiviral response. Retinoic acid-inducible gene I has been shown to contribute to virus-induced IFN production independent of the Toll-like receptor pathways in response to a variety of RNA viruses and double-stranded RNA. In the present study, we demonstrate that the NF-kappaB-inducible, anti-apoptotic protein A20 efficiently blocks RIG-I-mediated activation of NF-kappaB-, IRF-3-, and IRF-7-dependent promoters but only weakly interferes with TRIF-TLR-3-mediated IFN activation. Expression of A20 completely blocked CARD domain containing DeltaRIG-I-induced IRF-3 Ser-396 phosphorylation, homodimerization, and DNA binding. The level of A20 inhibition was upstream of the TBK1/IKKepsilon kinases that phosphorylate IRF3 and IRF7 and paradoxically, A20 selectively degraded the TRIF protein but not RIG-I. A20 possesses two ubiquitin-editing domains, an N-terminal deubiquitination domain and a C-terminal ubiquitin ligase domain consisting of seven zinc finger domains. Deletion of the N-terminal de-ubiquitination domain had no significant effect on the inhibitory effect of A20, whereas deletion or mutation of zinc finger motif 7 ablated the inhibitory function of A20 on IRF- or NF-kappaB-mediated gene expression. Furthermore, cells stably expressing the active form of RIG-I induced an antiviral state that interfered with replication of vesicular stomatitis virus, an effect that was reversed by stable co-expression of A20. These results suggest that the virus-inducible, NF-kappaB-dependent activation of A20 functions as a negative regulator of RIG-I-mediated induction of the antiviral state.

Negative regulation of the retinoic acid-inducible gene I-induced antiviral state by the ubiquitin-editing protein A20. Publishing Authors By Initials

R Lin,L Yang,P Nakhaei,Q Sun,E Sharif-Askari,I Julkunen,J Hiscott,

For similar zinc fingers research abstracts see: zinc fingers research

PUBMED ID PMID:

MEDLINE DATE:

Negative regulation of the retinoic acid-inducible gene I-induced antiviral state by the ubiquitin-editing protein A20. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of biological chemistry

VOLUME: 281

Page Numbers: 2095-103

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 23

MONTH: 11

YEAR: 2005

Negative regulation of the retinoic acid-inducible gene I-induced antiviral state by the ubiquitin-editing protein A20. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Negative regulation of the retinoic acid-inducible gene I-induced antiviral state by the ubiquitin-editing protein A20. Keywords Mesh Terms:

KEYWORDS: Zinc Fingers

MESH TERMS: metabolism

Chemical & Substance for Abstract: Negative regulation of the retinoic acid-inducible gene I-induced antiviral state by the ubiquitin-editing protein A20. Information

Substance Name: Ubiquitin-Protein Ligases

Registry Number: EC 6.3.2.19

Grant and Affiliation Information for Negative regulation of the retinoic acid-inducible gene I-induced antiviral state by the ubiquitin-editing protein A20.

AFFILIATION: Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, and Department of Microbiology, McGill University, Montreal, Quebec H3T 1E2, Canada. rongtuan.lin@mcgill.ca

Country: United States

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: J Biol Chem

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Negative regulation of the retinoic acid-inducible gene I-induced antiviral state by the ubiquitin-editing protein A20 Related Publications

• Chemical targeting of the innate antiviral response by histone deacetylase inhibitors renders refractory cancers sensitive to viral oncolysis.
• Convergence of the NF-kappaB and IRF pathways in the regulation of the innate antiviral response.
• Cytokeratin subtyping to distinguish reactive and neoplastic RPE cells.
• Health services in four isolated districts in Nova Scotia.
• Histological findings of a choroidal neovascular membrane removed at the time of macular translocation in a patient previously treated with intravitreal bevacizumab treatment (Avastin).
• Human papillomavirus in pterygium.
• Negative regulation of the retinoic acid-inducible gene I-induced antiviral state by the ubiquitin-editing protein A20.
• Neoplastic transformation of ciliary body epithelium is associated with loss of opticin expression.
• RIG-I has guts: identification of a role for RIG-I in colitis development.
• SDF1-alpha is associated with VEGFR-2 in human choroidal neovascularisation.
• Targeting the apoptotic pathway with BCL-2 inhibitors sensitizes primary chronic lymphocytic leukemia cells to vesicular stomatitis virus-induced oncolysis.
• Temporal pterygium: benign or not?
• Ub Surprised: Viral Ovarian Tumor Domain Proteases Remove Ubiquitin and ISG15 Conjugates.
• Vesicular stomatitis virus oncolysis of T lymphocytes requires cell cycle entry and translation initiation.