• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

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

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.

Pubmed ID: 21743479

Authors

  • Tun-Kyi A
  • Finn G
  • Greenwood A
  • Nowak M
  • Lee TH
  • Asara JM
  • Tsokos GC
  • Fitzgerald K
  • Israel E
  • Li X
  • Exley M
  • Nicholson LK
  • Lu KP

Journal

Nature immunology

Publication Data

August 20, 2011

Associated Grants

  • Agency: NIA NIH HHS, Id: AG029385
  • Agency: NIDDK NIH HHS, Id: DK066917
  • Agency: NIGMS NIH HHS, Id: GM058556
  • Agency: NIA NIH HHS, Id: R01 AG017870
  • Agency: NIA NIH HHS, Id: R01 AG017870-06A2
  • Agency: NIA NIH HHS, Id: R01 AG017870-07
  • Agency: NIA NIH HHS, Id: R01 AG017870-08
  • Agency: NIA NIH HHS, Id: R01 AG017870-09
  • Agency: NIA NIH HHS, Id: R01 AG017870-10
  • Agency: NIA NIH HHS, Id: R01 AG029385
  • Agency: NIA NIH HHS, Id: R01 AG029385-01
  • Agency: NIA NIH HHS, Id: R01 AG029385-02
  • Agency: NIA NIH HHS, Id: R01 AG029385-03
  • Agency: NIA NIH HHS, Id: R01 AG029385-04
  • Agency: NIA NIH HHS, Id: R01 AG029385-05
  • Agency: NIDDK NIH HHS, Id: R01 DK066917
  • Agency: NIDDK NIH HHS, Id: R01 DK066917-01
  • Agency: NIDDK NIH HHS, Id: R01 DK066917-02
  • Agency: NIDDK NIH HHS, Id: R01 DK066917-03
  • Agency: NIDDK NIH HHS, Id: R01 DK066917-04
  • Agency: NIDDK NIH HHS, Id: R01 DK066917-05
  • Agency: NIGMS NIH HHS, Id: R01 GM058556
  • Agency: NIGMS NIH HHS, Id: R01 GM058556-09A1
  • Agency: NIGMS NIH HHS, Id: R01 GM058556-10
  • Agency: NIGMS NIH HHS, Id: R01 GM058556-11
  • Agency: NIGMS NIH HHS, Id: R01 GM058556-12

Mesh Terms

  • Adaptive Immunity
  • Animals
  • Dendritic Cells
  • Immunity, Innate
  • Immunoblotting
  • Interferon Regulatory Factor-1
  • Interferon-beta
  • Interleukin-1 Receptor-Associated Kinases
  • Magnetic Resonance Spectroscopy
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Peptidylprolyl Isomerase
  • Phosphorylation
  • RNA
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Toll-Like Receptors