Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2010 May 19;29(10):1627-8.
doi: 10.1038/emboj.2010.79.

IRF-3 partners Bax in a viral-induced dance macabre

James E Vince  1 , Jurg Tschopp
Affiliations
Comment

IRF-3 partners Bax in a viral-induced dance macabre

James E Vince et al. EMBO J. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Models for MAVS-induced apoptosis. (A) IRF-3 transcription model. dsRNA transfection or that generated from replicating viruses such as VSV and SeV, binds RIG-I leading to MAVS activation on the mitochondrial outer membrane. TRAF3 recruits TBK1 and IKK-i resulting in IRF-3 phosphorylation and activation. Homodimers of IRF-3 (or IRF-3/IRF-7 heterodimers) induce transcription of the BH3-only proteins Noxa and Puma. These antagonize pro-survival Bcl-2 proteins such as Mcl-1 and Bcl-xL leading to Bax and Bak activation and loss of mitochondrial membrane integrity. Cytochrome C release causes apoptosome formation and cell death. (B) IRF-3 direct killing model. MAVS signalling results in IRF-3 activity as in (A), except instead of translocating to the nucleus, a portion of activated IRF-3 now binds cytosolic Bax through a BH3-like domain. IRF-3-induced Bax activity results in the efficient induction of apoptosis. (C) Anoikis model. Cell detachment results in apoptosis induction in many different primary cell types. DAP3, a proposed proponent in anoikis induction, binds to MAVS on cell detachment. MAVS recruits FADD and caspase-8 resulting in caspase-8 activation. Caspase-8 can activate downstream effector caspases (not shown), or cleave Bid to produce activated tBid. tBid antagonizes pro-survival Bcl-2 family members allowing Bax and Bak induced cell death to proceed.
See this image and copyright information in PMC

Comment on

References

    1. Besch R, Poeck H, Hohenauer T, Senft D, Häcker G, Berking C, Hornung V, Endres S, Ruzicka T, Rothenfusser S, Hartmann G (2009) Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon-independent apoptosis in human melanoma cells. J Clin Invest 119: 2399–2411 - PMC - PubMed
    1. Chattopadhyay S, Marques JT, Yamashita M, Peters KL, Smith K, Desai A, Williams BRG, Sen GC (2010) Viral apoptosis is induced by IRF-3-mediated activation of Bax. EMBO J 29: 1762–1773 - PMC - PubMed
    1. Chipuk JE, Kuwana T, Bouchier-Hayes L, Droin NM, Newmeyer DD, Schuler M, Green DR (2004) Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science 303: 1010–1014 - PubMed
    1. Giam M, Huang DCS, Bouillet P (2008) BH3-only proteins and their roles in programmed cell death. Oncogene 27(Suppl 1): S128–S136 - PubMed
    1. Heylbroeck C, Balachandran S, Servant MJ, DeLuca C, Barber GN, Lin R, Hiscott J (2000) The IRF-3 transcription factor mediates Sendai virus-induced apoptosis. J Virol 74: 3781–3792 - PMC - PubMed

Publication types