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000128029 1001_ $$aGlück, Selene$$b0
000128029 245__ $$aInnate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence.
000128029 260__ $$aNew York, NY$$bNature America$$c2017
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000128029 520__ $$aCellular senescence is triggered by various distinct stresses and characterized by a permanent cell cycle arrest. Senescent cells secrete a variety of inflammatory factors, collectively referred to as the senescence-associated secretory phenotype (SASP). The mechanism(s) underlying the regulation of the SASP remains incompletely understood. Here we define a role for innate DNA sensing in the regulation of senescence and the SASP. We find that cyclic GMP-AMP synthase (cGAS) recognizes cytosolic chromatin fragments in senescent cells. The activation of cGAS, in turn, triggers the production of SASP factors via stimulator of interferon genes (STING), thereby promoting paracrine senescence. We demonstrate that diverse stimuli of cellular senescence engage the cGAS-STING pathway in vitro and we show cGAS-dependent regulation of senescence following irradiation and oncogene activation in vivo. Our findings provide insights into the mechanisms underlying cellular senescence by establishing the cGAS-STING pathway as a crucial regulator of senescence and the SASP.
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000128029 650_7 $$2NLM Chemicals$$aChromatin
000128029 650_7 $$2NLM Chemicals$$aMPYS protein, mouse
000128029 650_7 $$2NLM Chemicals$$aMembrane Proteins
000128029 650_7 $$0EC 2.7.7.-$$2NLM Chemicals$$aMB21D1 protein, mouse
000128029 650_7 $$0EC 2.7.7.-$$2NLM Chemicals$$aNucleotidyltransferases
000128029 7001_ $$00000-0002-7750-9214$$aGuey, Baptiste$$b1
000128029 7001_ $$aGulen, Muhammet Fatih$$b2
000128029 7001_ $$aWolter, Katharina$$b3
000128029 7001_ $$0P:(DE-He78)e9f808a3a86f002da511eb9ae11f076f$$aKang, Tae-Won$$b4$$udkfz
000128029 7001_ $$aSchmacke, Niklas Arndt$$b5
000128029 7001_ $$aBridgeman, Anne$$b6
000128029 7001_ $$aRehwinkel, Jan$$b7
000128029 7001_ $$0P:(DE-He78)1ba2900406378e069d32db376c7818db$$aZender, Lars$$b8$$udkfz
000128029 7001_ $$00000-0002-8475-8999$$aAblasser, Andrea$$b9
000128029 773__ $$0PERI:(DE-600)1494945-3$$a10.1038/ncb3586$$gVol. 19, no. 9, p. 1061 - 1070$$n9$$p1061 - 1070$$tNature cell biology$$v19$$x1476-4679$$y2017
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