PIN1 mediated IRF3 degradation

Stable Identifier
R-HSA-936462
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
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PIN1 mediated IRF3 degradation
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PIN1 acts as a negative regulator of IFN induction. Its association with IRF3 leads to ubiquitin-mediated proteosomal degradation of IRF3. PIN1 on its own does not have ubiquitin activation, transfer or ligase activities. Exactly how this IRF3 degradation is achieved is unclear at present. Immunoprecipitation of ubiquitin followed by immunoblot analysis for IRF3 demonstrated that polyubiquitination of IRF3 was induced by RNA stimulation and that polyubiquitination was augmented by PIN1 expression and abrogated by expression of PIN1-specific shRNA. The transcription factor IRF3 is a target for ISGylation. Conjugation of ISG15 positively regulates IRF3 and thereby promotes induction of type I interferons. ISGylation of IRF3 prevents the binding of PIN1, a protein that promotes IRF3 ubiquitination and subsequent degradation.
Literature References
PubMed ID Title Journal Year
19125153 Inhibition of IRF3-dependent antiviral responses by cellular and viral proteins

Kawai, T, Akira, S, Tsuchida, T

Cell Res 2009
16715065 Pin-ning down immune responses to RNA viruses

Fitzgerald, KA, Severa, M, Goutagny, N

Nat Immunol 2006
16699525 Negative regulation of interferon-regulatory factor 3-dependent innate antiviral response by the prolyl isomerase Pin1

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

Nat Immunol 2006
Participants
Input
Output
Participates
as an event of
Catalyst Activity

ubiquitin protein ligase activity of unknown ligase [nucleoplasm]

Physical Entity
unknown ligase [nucleoplasm] (Homo sapiens)
Activity
ubiquitin protein ligase activity (GO:0061630)
This event is regulated
Negatively by
Regulator
ISGylated IRF3 [cytosol] (Homo sapiens)
Authored
Garapati, P V  (2010-08-02)
Reviewed
Akira, S  (2010-10-30)
Kawai, T  (2010-10-30)
Created
Garapati, P V  (2010-08-23)
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