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@ARTICLE{Smarduch:299001,
author = {S. Smarduch and S. D. Moreno-Velasquez and D. Ilic$^*$ and
S. Dadsena and R. Morant and A. Ciprinidis and G.
Pereira$^*$ and M. Binder$^*$ and A. J. García-Sáez and S.
P. Acebrón},
title = {{A} novel biosensor for the spatiotemporal analysis of
{STING} activation during innate immune responses to
ds{DNA}.},
journal = {The EMBO journal},
volume = {44},
number = {7},
issn = {0261-4189},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2025-00411},
pages = {2157-2182},
year = {2025},
note = {2025 Apr;44(7):2157-2182},
abstract = {The cGAS-STING signalling pathway has a central role in the
innate immune response to extrinsic and intrinsic sources of
cytoplasmic dsDNA. At the core of this pathway is
cGAS-dependent production of the intra- and extra-cellular
messenger cGAMP, which activates STING and leads to
IRF3-dependent expression of cytokines and interferons.
Despite its relevance to viral and bacterial infections,
cell death, and genome instability, the lack of specific
live-cell reporters has precluded spatiotemporal analyses of
cGAS-STING signalling. Here, we generate a fluorescent
biosensor termed SIRF (STING-IRF3), which reports on the
functional interaction between activated STING and IRF3 at
the Golgi. We show that cells harbouring SIRF react in a
time- and concentration-dependent manner both to STING
agonists and to microenvironmental cGAMP. We demonstrate
that the new biosensor is suitable for single-cell
characterisation of immune responses to HSV-1 infection,
mtDNA release upon apoptosis, or other sources of
cytoplasmic dsDNA. Furthermore, our results indicate that
STING signalling is not activated by ruptured micronuclei,
suggesting that other cytosolic pattern recognition
receptors underlie the interferon responses to chromosomal
instability.},
keywords = {Biosensor (Other) / Innate Immune Response (Other) /
Micronuclei (Other) / cGAMP (Other) / cGAS-STING Signalling
(Other)},
cin = {D430 / A180},
ddc = {570},
cid = {I:(DE-He78)D430-20160331 / I:(DE-He78)A180-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39984755},
doi = {10.1038/s44318-025-00370-y},
url = {https://inrepo02.dkfz.de/record/299001},
}