In:
eLife, eLife Sciences Publications, Ltd, Vol. 2 ( 2013-08-14)
Abstract:
The innate immune system can detect and destroy viruses, bacteria and other pathogens that enter the human body. In particular, inside cells, viral RNA can bind to and activate a protein called RIG-I. This protein switches on another protein, called MAVS, which can activate other copies of itself. These MAVS molecules then aggregate together on the membrane of mitochondria and send a signal that leads to the production of small proteins, called cytokines, which stimulate an inflammatory response and ultimately neutralize the virus. Although many of the proteins that are activated by MAVS in the innate immunity signaling pathway have been identified, precisely how MAVS transmits this signal is unknown. Now, Liu et al. explore how this protein can propagate signals in the innate immune response by monitoring activation of the transcription factors IRF3 and NF-κB, which transcribe cytokine genes. Previous studies have suggested that a protein known as ubiquitin is needed to activate RIG-I, and that this protein collaborates with MAVS to signal through the innate immunity pathway. Liu et al. found that a group of proteins including TRAF2, TRAF5, TRAF6 and LUBAC relay the antiviral signal by binding to MAVS. These so-called ‘E3 ligases’ string ubiquitin together in chains called polyubiquitin, which is essential for activating signaling after, or downstream of, MAVS; however, the association of these E3 ligases with MAVS also requires that multiple copies of MAVS cluster together. MAVS, the TRAF proteins and LUBAC collectively recruit other innate immunity pathway proteins to activate IRF3 and NF-κB, and thus transcription of the genes that control the innate immunity response. Together, these results show the intricate interplay of proteins needed to eliminate viruses from the body.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.00785.001
DOI:
10.7554/eLife.00785.002
DOI:
10.7554/eLife.00785.003
DOI:
10.7554/eLife.00785.004
DOI:
10.7554/eLife.00785.005
DOI:
10.7554/eLife.00785.006
DOI:
10.7554/eLife.00785.007
DOI:
10.7554/eLife.00785.008
DOI:
10.7554/eLife.00785.009
DOI:
10.7554/eLife.00785.010
DOI:
10.7554/eLife.00785.011
DOI:
10.7554/eLife.00785.012
DOI:
10.7554/eLife.00785.013
DOI:
10.7554/eLife.00785.014
DOI:
10.7554/eLife.00785.015
DOI:
10.7554/eLife.00785.016
DOI:
10.7554/eLife.00785.017
DOI:
10.7554/eLife.00785.018
DOI:
10.7554/eLife.00785.019
DOI:
10.7554/eLife.00785.020
DOI:
10.7554/eLife.00785.021
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2013
detail.hit.zdb_id:
2687154-3
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