PMID- 28720717
OWN - NLM
STAT- MEDLINE
DCOM- 20180305
LR  - 20231213
IS  - 1937-9145 (Electronic)
IS  - 1945-0877 (Linking)
VI  - 10
IP  - 488
DP  - 2017 Jul 18
TI  - STING is an essential mediator of the Ku70-mediated production of IFN-lambda1 in 
      response to exogenous DNA.
LID - eaah5054 [pii]
LID - 10.1126/scisignal.aah5054 [doi]
AB  - We previously identified Ku70, a subunit of a DNA repair protein complex, as a 
      cytosolic DNA sensor that induces the production of interferon-lambda1 (IFN-lambda1) by 
      human primary cells and cell lines. IFN-lambda1 is a type III IFN and has similar 
      antiviral activity to that of the type I IFNs (IFN-alpha and IFN-beta). We observed that 
      human embryonic kidney (HEK) 293T cells, which are deficient in the innate immune 
      adaptor protein STING (stimulator of IFN genes), did not produce IFN-lambda1 in 
      response to DNA unless they were reconstituted with STING. Conversely, parental 
      HEK 293 cells produced IFN-lambda1 after they were exposed to exogenous DNA; however, 
      when STING was knocked out in the HEK 293 cells through the CRISPR (clustered 
      regularly interspaced short palindromic repeats)/Cas9 genome editing system, they 
      lost this response. Through confocal microscopy, we demonstrated that endogenous 
      Ku70 was located in the nucleus and then translocated to the cytoplasm upon DNA 
      exposure to form a complex with STING. Additionally, the DNA binding domain of 
      Ku70 was essential for formation of the Ku70-STING complex. Knocking down STING 
      in primary human macrophages inhibited their ability to produce IFN-lambda1 in 
      response to transfection with DNA or infection with the DNA virus HSV-2 (herpes 
      simplex virus-2). Together, these data suggest that STING mediates the 
      Ku70-mediated IFN-lambda1 innate immune response to exogenous DNA or DNA virus 
      infection.
CI  - Copyright (c) 2017 The Authors, some rights reserved; exclusive licensee American 
      Association for the Advancement of Science. No claim to original U.S. Government 
      Works.
FAU - Sui, Hongyan
AU  - Sui H
AUID- ORCID: 0000-0002-4341-0929
AD  - Laboratory of Human Retrovirology and Immunoinformatics, Applied and 
      Developmental Research Directorate, Leidos Biomedical Research Inc., Frederick 
      National Laboratory for Cancer Research, Frederick, MD 21702, USA.
FAU - Zhou, Ming
AU  - Zhou M
AD  - Laboratory of Proteomics and Analytical Technologies, Cancer Research Technology 
      Program, Leidos Biomedical Research Inc., Frederick National Laboratory for 
      Cancer Research, Frederick, MD 21702, USA.
FAU - Imamichi, Hiromi
AU  - Imamichi H
AD  - Laboratory of Immunoregulation, National Institute of Allergy and Infectious 
      Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
FAU - Jiao, Xiaoli
AU  - Jiao X
AUID- ORCID: 0000-0001-6385-7835
AD  - Laboratory of Human Retrovirology and Immunoinformatics, Applied and 
      Developmental Research Directorate, Leidos Biomedical Research Inc., Frederick 
      National Laboratory for Cancer Research, Frederick, MD 21702, USA.
FAU - Sherman, Brad T
AU  - Sherman BT
AUID- ORCID: 0000-0001-5815-7359
AD  - Laboratory of Human Retrovirology and Immunoinformatics, Applied and 
      Developmental Research Directorate, Leidos Biomedical Research Inc., Frederick 
      National Laboratory for Cancer Research, Frederick, MD 21702, USA.
FAU - Lane, H Clifford
AU  - Lane HC
AD  - Laboratory of Immunoregulation, National Institute of Allergy and Infectious 
      Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
FAU - Imamichi, Tomozumi
AU  - Imamichi T
AUID- ORCID: 0000-0002-1474-1796
AD  - Laboratory of Human Retrovirology and Immunoinformatics, Applied and 
      Developmental Research Directorate, Leidos Biomedical Research Inc., Frederick 
      National Laboratory for Cancer Research, Frederick, MD 21702, USA. 
      timamichi@mail.nih.gov.
LA  - eng
PT  - Journal Article
DEP - 20170718
PL  - United States
TA  - Sci Signal
JT  - Science signaling
JID - 101465400
RN  - 0 (DNA, Viral)
RN  - 0 (interferon-lambda, human)
RN  - 0 (Interleukins)
RN  - 0 (Membrane Proteins)
RN  - 0 (STING1 protein, human)
RN  - 9008-11-1 (Interferons)
RN  - EC 3.6.4.12 (XRCC5 protein, human)
RN  - EC 4.2.99.- (Ku Autoantigen)
SB  - IM
MH  - DNA, Viral/immunology
MH  - HEK293 Cells
MH  - Humans
MH  - Immunity, Innate
MH  - Interferons/*metabolism
MH  - Interleukins/*immunology
MH  - Ku Autoantigen/*metabolism
MH  - Macrophages/*immunology
MH  - Membrane Proteins/*metabolism
MH  - Protein Transport
EDAT- 2017/07/20 06:00
MHDA- 2018/03/06 06:00
CRDT- 2017/07/20 06:00
PHST- 2017/07/20 06:00 [entrez]
PHST- 2017/07/20 06:00 [pubmed]
PHST- 2018/03/06 06:00 [medline]
AID - 10/488/eaah5054 [pii]
AID - 10.1126/scisignal.aah5054 [doi]
PST - epublish
SO  - Sci Signal. 2017 Jul 18;10(488):eaah5054. doi: 10.1126/scisignal.aah5054.