Matches in SemOpenAlex for { <https://semopenalex.org/work/W3011301901> ?p ?o ?g. }
- W3011301901 abstract "ABSTRACT Mutations in the p53 tumor suppressor occur very frequently in human cancer. Often, such mutations lead to the constitutive overproduction of mutant p53 (mtp53) proteins, which can exert a cancer-promoting gain-of-function (GOF). We have identified a novel mechanism by which mtp53 controls both cell-autonomous and non-cell autonomous signaling to promote cancer cell survival and suppress tumor immune surveillance. Mtp53 interferes with the function of the cytoplasmic DNA sensing machinery, cGAS-STING-TBK1-IRF3, that controls the activation of the innate immune response. We find that mtp53, but not wildtype p53, binds to TANK binding protein kinase (TBK1) and inhibits both its basal and agonist-induced activity. The association of mtp53 with TBK1 prevents the formation of a trimeric complex between TBK1-STING-IRF3, which is required for activation, nuclear translocation and transcriptional activity of IRF3. Mtp53 knockdown restores TBK1 activity, resulting in the transcriptional induction of IRF3 target genes and IRF3-dependent apoptosis. Furthermore, inactivation of innate immune signaling by mtp53 alters cytokine production resulting in immune evasion. Restored TBK1 signaling was sufficient to bypass mtp53 and reactivate cell-autonomous and non-cell autonomous tumor control. Thus, overriding mtp53’s inhibition of this cytosolic DNA sensing pathway may ultimately lead to restored immune cell function and cancer cell eradication." @default.
- W3011301901 created "2020-03-23" @default.
- W3011301901 creator A5011655832 @default.
- W3011301901 creator A5043198099 @default.
- W3011301901 creator A5048495207 @default.
- W3011301901 creator A5049433901 @default.
- W3011301901 creator A5079942422 @default.
- W3011301901 creator A5084594436 @default.
- W3011301901 creator A5087199070 @default.
- W3011301901 creator A5090771254 @default.
- W3011301901 date "2020-03-13" @default.
- W3011301901 modified "2023-10-17" @default.
- W3011301901 title "Mutant p53 suppresses innate immune signaling to promote tumorigenesis" @default.
- W3011301901 cites W1558701786 @default.
- W3011301901 cites W1965827039 @default.
- W3011301901 cites W1968178474 @default.
- W3011301901 cites W1992995822 @default.
- W3011301901 cites W2047365750 @default.
- W3011301901 cites W2069452349 @default.
- W3011301901 cites W2077145482 @default.
- W3011301901 cites W2079045730 @default.
- W3011301901 cites W2083147016 @default.
- W3011301901 cites W2088441464 @default.
- W3011301901 cites W2099610218 @default.
- W3011301901 cites W2104397341 @default.
- W3011301901 cites W2119885778 @default.
- W3011301901 cites W2132413371 @default.
- W3011301901 cites W2138657695 @default.
- W3011301901 cites W2165259537 @default.
- W3011301901 cites W2170163416 @default.
- W3011301901 cites W2187527489 @default.
- W3011301901 cites W2220279767 @default.
- W3011301901 cites W2237797200 @default.
- W3011301901 cites W2331626130 @default.
- W3011301901 cites W2410798112 @default.
- W3011301901 cites W2414978187 @default.
- W3011301901 cites W2525369565 @default.
- W3011301901 cites W2586927752 @default.
- W3011301901 cites W2588219496 @default.
- W3011301901 cites W2693925639 @default.
- W3011301901 cites W2750976328 @default.
- W3011301901 cites W2762611634 @default.
- W3011301901 cites W2783667606 @default.
- W3011301901 cites W2791512052 @default.
- W3011301901 cites W2811281203 @default.
- W3011301901 cites W2834234275 @default.
- W3011301901 cites W2884728705 @default.
- W3011301901 cites W2891405227 @default.
- W3011301901 cites W2891731267 @default.
- W3011301901 cites W2906160139 @default.
- W3011301901 cites W2913440788 @default.
- W3011301901 cites W2913665794 @default.
- W3011301901 cites W2921875691 @default.
- W3011301901 cites W2949439905 @default.
- W3011301901 cites W2952255603 @default.
- W3011301901 cites W2954248267 @default.
- W3011301901 cites W2964649258 @default.
- W3011301901 cites W2965035617 @default.
- W3011301901 cites W2965576600 @default.
- W3011301901 cites W2995171541 @default.
- W3011301901 cites W4232186666 @default.
- W3011301901 doi "https://doi.org/10.1101/2020.03.12.989384" @default.
- W3011301901 hasPublicationYear "2020" @default.
- W3011301901 type Work @default.
- W3011301901 sameAs 3011301901 @default.
- W3011301901 citedByCount "2" @default.
- W3011301901 countsByYear W30113019012020 @default.
- W3011301901 countsByYear W30113019012021 @default.
- W3011301901 crossrefType "posted-content" @default.
- W3011301901 hasAuthorship W3011301901A5011655832 @default.
- W3011301901 hasAuthorship W3011301901A5043198099 @default.
- W3011301901 hasAuthorship W3011301901A5048495207 @default.
- W3011301901 hasAuthorship W3011301901A5049433901 @default.
- W3011301901 hasAuthorship W3011301901A5079942422 @default.
- W3011301901 hasAuthorship W3011301901A5084594436 @default.
- W3011301901 hasAuthorship W3011301901A5087199070 @default.
- W3011301901 hasAuthorship W3011301901A5090771254 @default.
- W3011301901 hasBestOaLocation W30113019011 @default.
- W3011301901 hasConcept C121608353 @default.
- W3011301901 hasConcept C136449434 @default.
- W3011301901 hasConcept C156155473 @default.
- W3011301901 hasConcept C173396325 @default.
- W3011301901 hasConcept C190283241 @default.
- W3011301901 hasConcept C195794163 @default.
- W3011301901 hasConcept C203014093 @default.
- W3011301901 hasConcept C2780209191 @default.
- W3011301901 hasConcept C502942594 @default.
- W3011301901 hasConcept C54355233 @default.
- W3011301901 hasConcept C55493867 @default.
- W3011301901 hasConcept C555283112 @default.
- W3011301901 hasConcept C62478195 @default.
- W3011301901 hasConcept C86803240 @default.
- W3011301901 hasConcept C8891405 @default.
- W3011301901 hasConcept C90934575 @default.
- W3011301901 hasConcept C95444343 @default.
- W3011301901 hasConceptScore W3011301901C121608353 @default.
- W3011301901 hasConceptScore W3011301901C136449434 @default.
- W3011301901 hasConceptScore W3011301901C156155473 @default.
- W3011301901 hasConceptScore W3011301901C173396325 @default.
- W3011301901 hasConceptScore W3011301901C190283241 @default.