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.
Kawai, T, Akira, S, Tsuchida, T
Fitzgerald, KA, Severa, M, Goutagny, N
Yamamoto, N, Fujita, T, Ryo, A, Saitoh, T, Yamaoka, S, Lu, KP, Yamamoto, M, Tun-Kyi, A, Akira, S, Finn, G
ubiquitin protein ligase activity of unknown ligase [nucleoplasm]
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