Attenuation of cGAS/STING activity during mitosis.

Autor:	Uhlorn BL; Cancer Biology Graduate Interdisciplinary Program, The University of Arizona, Tucson, AZ, USA., Gamez ER; Department of Physiology, The University of Arizona, Tucson, AZ, USA., Li S; Department of Immunobiology, The University of Arizona, Tucson, AZ, USA., Campos SK; Cancer Biology Graduate Interdisciplinary Program, The University of Arizona, Tucson, AZ, USA skcampos@email.arizona.edu.; Department of Immunobiology, The University of Arizona, Tucson, AZ, USA.; BIO5 Institute, The University of Arizona, Tucson, AZ, USA.; Department of Molecular and Cellular Biology, The University of Arizona, Tucson, AZ, USA.
Jazyk:	angličtina
Zdroj:	Life science alliance [Life Sci Alliance] 2020 Jul 13; Vol. 3 (9). Date of Electronic Publication: 2020 Jul 13 (Print Publication: 2020).
DOI:	10.26508/lsa.201900636
Abstrakt:	The innate immune system recognizes cytosolic DNA associated with microbial infections and cellular stress via the cGAS/STING pathway, leading to activation of phospho-IRF3 and downstream IFN-I and senescence responses. To prevent hyperactivation, cGAS/STING is presumed to be nonresponsive to chromosomal self-DNA during open mitosis, although specific regulatory mechanisms are lacking. Given a role for the Golgi in STING activation, we investigated the state of the cGAS/STING pathway in interphase cells with artificially vesiculated Golgi and in cells arrested in mitosis. We find that whereas cGAS activity is impaired through interaction with mitotic chromosomes, Golgi integrity has little effect on the enzyme's production of cGAMP. In contrast, STING activation in response to either foreign DNA (cGAS-dependent) or exogenous cGAMP is impaired by a vesiculated Golgi. Overall, our data suggest a secondary means for cells to limit potentially harmful cGAS/STING responses during open mitosis via natural Golgi vesiculation. (© 2020 Uhlorn et al.)
Databáze:	MEDLINE
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