Journal Article DKFZ-2017-04051

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Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence.

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2017
Nature America New York, NY

Nature cell biology 19(9), 1061 - 1070 () [10.1038/ncb3586]
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Abstract: 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.

Keyword(s): Chromatin ; MPYS protein, mouse ; Membrane Proteins ; MB21D1 protein, mouse ; Nucleotidyltransferases

Classification:

Contributing Institute(s):
  1. Translationale Gastrointestinale Onkologie (V076)
  2. DKTK Tübingen (L801)
Research Program(s):
  1. 319H - Addenda (POF3-319H) (POF3-319H)

Appears in the scientific report 2017
Database coverage:
Medline ; BIOSIS Previews ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 15 ; JCR ; NCBI Molecular Biology Database ; NationallizenzNationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection
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 Record created 2017-10-05, last modified 2024-02-28



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