TY  - JOUR
AU  - Glück, Selene
AU  - Guey, Baptiste
AU  - Gulen, Muhammet Fatih
AU  - Wolter, Katharina
AU  - Kang, Tae-Won
AU  - Schmacke, Niklas Arndt
AU  - Bridgeman, Anne
AU  - Rehwinkel, Jan
AU  - Zender, Lars
AU  - Ablasser, Andrea
TI  - Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence.
JO  - Nature cell biology
VL  - 19
IS  - 9
SN  - 1476-4679
CY  - New York, NY
PB  - Nature America
M1  - DKFZ-2017-04051
SP  - 1061 - 1070
PY  - 2017
AB  - Cellular senescence is triggered by various distinct stresses and characterized by a permanent cell cycle arrest. Senescent cells secrete a variety of inflammatory factors, collectively referred to as the senescence-associated secretory phenotype (SASP). The mechanism(s) underlying the regulation of the SASP remains incompletely understood. Here we define a role for innate DNA sensing in the regulation of senescence and the SASP. We find that cyclic GMP-AMP synthase (cGAS) recognizes cytosolic chromatin fragments in senescent cells. The activation of cGAS, in turn, triggers the production of SASP factors via stimulator of interferon genes (STING), thereby promoting paracrine senescence. We demonstrate that diverse stimuli of cellular senescence engage the cGAS-STING pathway in vitro and we show cGAS-dependent regulation of senescence following irradiation and oncogene activation in vivo. Our findings provide insights into the mechanisms underlying cellular senescence by establishing the cGAS-STING pathway as a crucial regulator of senescence and the SASP.
KW  - Chromatin (NLM Chemicals)
KW  - MPYS protein, mouse (NLM Chemicals)
KW  - Membrane Proteins (NLM Chemicals)
KW  - MB21D1 protein, mouse (NLM Chemicals)
KW  - Nucleotidyltransferases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:28759028
DO  - DOI:10.1038/ncb3586
UR  - https://inrepo02.dkfz.de/record/128029
ER  -