Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313373335> ?p ?o ?g. }
Showing items 1 to 56 of
56
with 100 items per page.
- W4313373335 endingPage "162.5" @default.
- W4313373335 startingPage "162.5" @default.
- W4313373335 abstract "Abstract The cGAS-STING pathway, a crucial component of innate immunity, recognizes viral DNA in the cytosol. cGAS binds dsDNA and catalyzes the production of the second messenger cGAMP, resulting in the expression of Type I interferons and other pro-inflammatory genes. To prevent autoimmunity, activation of cGAS by cytosolic self-DNA is normally counteracted by the cytosolic nuclease TREX1. In many chromosomally instable cancers, cytosolic self-DNA accumulates as DNA bridges or micronuclei (MN), whose nuclear envelopes are prone to rupture, exposing contained DNA to the cytosol. cGAS activation at ruptured MN is implicated in anti-tumor immunity. However, mechanisms regulating cGAS activation at ruptured MN are yet unknown. Here, we show that TREX1 partially degrades chromosomal DNA in the cytosol to suppress cGAS activation. We observed localization of cGAS and TREX1 to ruptured MN and DNA bridges, strongly suggesting an unknown role for TREX1 in regulating cGAS activation in cancer. After induction of MN or DNA bridge formation, TREX1 KO causes dramatic increases in cGAMP production and cGAS-STING pathway signaling. Furthermore, ruptured MN exhibit TREX1-dependent DNA damage and ssDNA foci. TREX1 is bound to the ER, which is known to invade ruptured MN. We found that an ER binding mutant of TREX1 does not localize to MN anymore and was not able to rescue the TREX1 KO phenotype, suggesting a role for the ER to recruit TREX1 to MN. In summary, we propose that TREX1 enters MN as a consequence of nuclear envelope rupture to partially degrade DNA, thereby suppressing cGAS activation. By eliminating the immunogenic potential of these DNA species, TREX1 may dampen anti-tumor immunity and thereby help cancer cells escape the immune system." @default.
- W4313373335 created "2023-01-06" @default.
- W4313373335 creator A5022902421 @default.
- W4313373335 creator A5052921844 @default.
- W4313373335 creator A5075531584 @default.
- W4313373335 date "2020-05-01" @default.
- W4313373335 modified "2023-09-27" @default.
- W4313373335 title "TREX1-induced chromosome fragmentation at the interface of innate immunity and genomic instability" @default.
- W4313373335 doi "https://doi.org/10.4049/jimmunol.204.supp.162.5" @default.
- W4313373335 hasPublicationYear "2020" @default.
- W4313373335 type Work @default.
- W4313373335 citedByCount "0" @default.
- W4313373335 crossrefType "journal-article" @default.
- W4313373335 hasAuthorship W4313373335A5022902421 @default.
- W4313373335 hasAuthorship W4313373335A5052921844 @default.
- W4313373335 hasAuthorship W4313373335A5075531584 @default.
- W4313373335 hasConcept C136449434 @default.
- W4313373335 hasConcept C143425029 @default.
- W4313373335 hasConcept C181199279 @default.
- W4313373335 hasConcept C54355233 @default.
- W4313373335 hasConcept C552990157 @default.
- W4313373335 hasConcept C55493867 @default.
- W4313373335 hasConcept C86803240 @default.
- W4313373335 hasConcept C8891405 @default.
- W4313373335 hasConcept C95444343 @default.
- W4313373335 hasConcept C98539663 @default.
- W4313373335 hasConceptScore W4313373335C136449434 @default.
- W4313373335 hasConceptScore W4313373335C143425029 @default.
- W4313373335 hasConceptScore W4313373335C181199279 @default.
- W4313373335 hasConceptScore W4313373335C54355233 @default.
- W4313373335 hasConceptScore W4313373335C552990157 @default.
- W4313373335 hasConceptScore W4313373335C55493867 @default.
- W4313373335 hasConceptScore W4313373335C86803240 @default.
- W4313373335 hasConceptScore W4313373335C8891405 @default.
- W4313373335 hasConceptScore W4313373335C95444343 @default.
- W4313373335 hasConceptScore W4313373335C98539663 @default.
- W4313373335 hasIssue "1_Supplement" @default.
- W4313373335 hasLocation W43133733351 @default.
- W4313373335 hasOpenAccess W4313373335 @default.
- W4313373335 hasPrimaryLocation W43133733351 @default.
- W4313373335 hasRelatedWork W2000561387 @default.
- W4313373335 hasRelatedWork W2015707024 @default.
- W4313373335 hasRelatedWork W2028633235 @default.
- W4313373335 hasRelatedWork W2038922087 @default.
- W4313373335 hasRelatedWork W2063893008 @default.
- W4313373335 hasRelatedWork W2791484806 @default.
- W4313373335 hasRelatedWork W2820141138 @default.
- W4313373335 hasRelatedWork W2938858873 @default.
- W4313373335 hasRelatedWork W2946210150 @default.
- W4313373335 hasRelatedWork W4200007513 @default.
- W4313373335 hasVolume "204" @default.
- W4313373335 isParatext "false" @default.
- W4313373335 isRetracted "false" @default.
- W4313373335 workType "article" @default.