例如："lncRNA", "apoptosis", "WRKY"

Modular Architecture of the STING C-Terminal Tail Allows Interferon and NF-κB Signaling Adaptation.

Cell Rep. 2019 Apr 23;27(4):1165-1175.e5
Carina C de Oliveira Mann 1 , Megan H Orzalli 2 , David S King 3 , Jonathan C Kagan 2 , Amy S Y Lee 4 , Philip J Kranzusch 5
Carina C de Oliveira Mann 1 , Megan H Orzalli 2 , David S King 3 , Jonathan C Kagan 2 , Amy S Y Lee 4 , Philip J Kranzusch 5
+ et al

[No authors listed]

Author information
  • 1 Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
  • 2 Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
  • 3 HHMI Mass Spectrometry Laboratory, University of California, Berkeley, Berkeley, California 94720, USA.
  • 4 Department of Biology, Brandeis University, Waltham, MA 02453, USA. Electronic address: amysylee@brandeis.edu.
  • 5 Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Parker Institute for Cancer Immunotherapy at Dana-Farber Cancer Institute, Boston, MA 02115, USA. Electronic address: philip_kranzusch@dfci.harvard.edu.

摘要

Stimulator of interferon genes (STING) is a key regulator of type I interferon and pro-inflammatory responses during infection, cellular stress, and cancer. Here, we reveal a mechanism for how STING balances activation of IRF3- and NF-κB-dependent transcription and discover that acquisition of discrete signaling modules in the vertebrate STING C-terminal tail (CTT) shapes downstream immunity. As a defining example, we identify a motif appended to the CTT of zebrafish STING that inverts the typical vertebrate signaling response and results in dramatic NF-κB activation and weak IRF3-interferon signaling. We determine a co-crystal structure that explains how this CTT sequence recruits TRAF6 as a new binding partner and demonstrate that the minimal motif is sufficient to reprogram human STING and immune activation in macrophage cells. Together, our results define the STING CTT as a linear signaling hub that can acquire modular motifs to readily adapt downstream immunity.

KEYWORDS: IRF3, NF-κB, STING, TRAF6, cGAS, innate immunity

© 2017 biocloud.net版权所有 ICP证：京10042835号