Interaction of PIN1 with p-IRF3

Stable Identifier
R-HSA-936380
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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Two cluster of serine residues in the C-terminus of IRF3 are essential for its activation. Cluster 1, comprising Ser385 and Ser386, is essential for the formation of IRF3 dimers. The second cluster include a series of serine and threonine residues between Ser396 and Ser405. Phosphorylation of residues in both clusters has been noted in response to virus infection and dsRNA treatment, and the IKKi/TBK1 kinase complex has been shown to phosphorylate both clusters.
Yamaoka et al has shown that IRF3 is also phosphorylated on Ser339 after dsRNA stimulation, however this phosphorylation is associated with destabilization rather than activation of IRF3. This Ser339 precedes a proline residue 340 (Pro340) and this serine-proline motif acts as a binding site for the protein PIN1, a peptidyl-prolyl-isomerase. PIN1 consist of two distinct domains, a short N-terminal WW domain and a C-terminal catalytic domain. The WW domain of PIN1 is involved in binding the ser339-pro340 region. Yamaoka et al showed that exogenous expression of PIN1 suppresses IRF3 activation and type I interferon production and, conversely, that siRNA silencing of PIN1 leads to enhancement of IRF3 activation and IFNB production.

Literature References
PubMed ID Title Journal Year
16715065 Pin-ning down immune responses to RNA viruses

Goutagny, N, Severa, M, Fitzgerald, KA

Nat Immunol 2006
19125153 Inhibition of IRF3-dependent antiviral responses by cellular and viral proteins

Tsuchida, T, Kawai, T, Akira, S

Cell Res 2009
16699525 Negative regulation of interferon-regulatory factor 3-dependent innate antiviral response by the prolyl isomerase Pin1

Saitoh, T, Tun-Kyi, A, Ryo, A, Yamamoto, M, Finn, G, Fujita, T, Akira, S, Yamamoto, N, Lu, KP, Yamaoka, S

Nat Immunol 2006
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