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Publication : Essential role for the prolyl isomerase Pin1 in Toll-like receptor signaling and type I interferon-mediated immunity.

First Author  Tun-Kyi A Year  2011
Journal  Nat Immunol Volume  12
Issue  8 Pages  733-41
PubMed ID  21743479 Mgi Jnum  J:174420
Mgi Id  MGI:5086021 Doi  10.1038/ni.2069
Citation  Tun-Kyi A, et al. (2011) Essential role for the prolyl isomerase Pin1 in Toll-like receptor signaling and type I interferon-mediated immunity. Nat Immunol 12(8):733-41
abstractText  Toll-like receptors (TLRs) shape innate and adaptive immunity to microorganisms. The enzyme IRAK1 transduces signals from TLRs, but mechanisms for its activation and regulation remain unknown. We found here that TLR7 and TLR9 activated the isomerase Pin1, which then bound to IRAK1; this resulted in activation of IRAK1 and facilitated its release from the receptor complex to activate the transcription factor IRF7 and induce type I interferons. Consequently, Pin1-deficient cells and mice failed to mount TLR-mediated, interferon-dependent innate and adaptive immune responses. Given the critical role of aberrant activation of IRAK1 and type I interferons in various immune diseases, controlling IRAK1 activation via inhibition of Pin1 may represent a useful therapeutic approach.
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