PIN1 mediated IRF3 degradation

Stable Identifier
R-HSA-936462
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
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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.

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
Participants
Participates
Catalyst Activity

ubiquitin protein ligase activity of unknown ligase [nucleoplasm]

This event is regulated
Negatively by
Regulator
Summation

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.

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