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Sci. Signal., 29 May 2012
Vol. 5, Issue 226, p. re3
[DOI: 10.1126/scisignal.2003124]

REVIEWS

Structural Insights into the Assembly of Large Oligomeric Signalosomes in the Toll-Like Receptor–Interleukin-1 Receptor Superfamily

Ryan Ferrao1,2, Jixi Li1, Elisa Bergamin1, and Hao Wu1,2*

1 Department of Biochemistry, Weill Cornell Medical College, New York, NY 10021, USA.
2 Weill Cornell Graduate School of Medical Sciences, New York, NY 10021, USA.

Gloss: Innate immunity and inflammation constitute the initial responses to injury or infection. Toll-like receptors (TLRs) participate in the recognition of invading viruses and microorganisms by recognizing molecules that are either not present or uncommon in the host cell, known as pathogen-associated molecular patterns (PAMPs). The potent proinflammatory cytokine interleukin-1β (IL-1β) is recognized by IL-1 receptor I (IL-1RI) and the co-receptor IL-1RAcP. Upon recognition of their cognate ligand, these receptors initiate a shared cytosolic signaling cascade. Structural studies have begun to reveal that these signaling cascades coalesce into large oligomeric signaling complexes or "signalosomes" for signal propagation. Through phosphorylation and ubiquitination reactions, this signaling results in the activation of the inhibitor of nuclear factor {kappa}B (NF-{kappa}B) kinase (IKK), which then phosphorylates the NF-{kappa}B inhibitor I{kappa}B, promoting its degradation. Degradation of I{kappa}B enables the transcription factor NF-{kappa}B to translocate to the nucleus and promote the expression of genes whose products are involved in innate and adaptive immunity, inflammation, cell survival, and proliferation.

* Corresponding author. E-mail: haowu{at}med.cornell.edu

Citation: R. Ferrao, J. Li, E. Bergamin, H. Wu, Structural Insights into the Assembly of Large Oligomeric Signalosomes in the Toll-Like Receptor–Interleukin-1 Receptor Superfamily. Sci. Signal. 5, re3 (2012).

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