Matches in SemOpenAlex for { <https://semopenalex.org/work/W4306913925> ?p ?o ?g. }
- W4306913925 endingPage "2132" @default.
- W4306913925 startingPage "2114" @default.
- W4306913925 abstract "Abstract MPYS/STING (stimulator of IFN genes) senses cyclic dinucleotides (CDNs), generates type I IFNs, and plays a critical role in infection, inflammation, and cancer. In this study, analyzing genotype and haplotype data from the 1000 Genomes Project, we found that the R71H-G230A-R293Q (HAQ) MPYS allele frequency increased 57-fold in East Asians compared with sub-Saharan Africans. Meanwhile, the G230A-R293Q (AQ) allele frequency decreased by 98% in East Asians compared with sub-Saharan Africans. We propose that the HAQ and AQ alleles underwent a natural selection during the out-of-Africa migration. We used mouse models of HAQ and AQ to investigate the underlying mechanism. We found that the mice carrying the AQ allele, which disappeared in East Asians, had normal CDN–type I IFN responses. Adult AQ mice, however, had less fat mass than did HAQ or wild-type mice on a chow diet. AQ epididymal adipose tissue had increased regulatory T cells and M2 macrophages with protein expression associated with enhanced fatty acid oxidation. Conditional knockout mice and adoptive cell transfer indicate a macrophage and regulatory T cell–intrinsic role of MPYS in fatty acid metabolism. Mechanistically, AQ/IFNAR1−/− mice had a similar lean phenotype as for the AQ mice. MPYS intrinsic tryptophan fluorescence revealed that the R71H change increased MPYS hydrophilicity. Lastly, we found that the second transmembrane (TM) and the TM2–TM3 linker region of MPYS interact with activated fatty acid, fatty acyl–CoA. In summary, studying the evolution of the human MPYS gene revealed an MPYS function in modulating fatty acid metabolism that may be critical during the out-of-Africa migration." @default.
- W4306913925 created "2022-10-21" @default.
- W4306913925 creator A5002779994 @default.
- W4306913925 creator A5003342935 @default.
- W4306913925 creator A5011962133 @default.
- W4306913925 creator A5018985683 @default.
- W4306913925 creator A5024699628 @default.
- W4306913925 creator A5047788847 @default.
- W4306913925 creator A5066665904 @default.
- W4306913925 creator A5069721146 @default.
- W4306913925 date "2022-12-01" @default.
- W4306913925 modified "2023-10-18" @default.
- W4306913925 title "MPYS Modulates Fatty Acid Metabolism and Immune Tolerance at Homeostasis Independent of Type I IFNs" @default.
- W4306913925 cites W1509641772 @default.
- W4306913925 cites W1556918753 @default.
- W4306913925 cites W1749037810 @default.
- W4306913925 cites W1763805809 @default.
- W4306913925 cites W1838882977 @default.
- W4306913925 cites W1929156901 @default.
- W4306913925 cites W1983406510 @default.
- W4306913925 cites W1997722194 @default.
- W4306913925 cites W2009610362 @default.
- W4306913925 cites W2010957046 @default.
- W4306913925 cites W2015310325 @default.
- W4306913925 cites W2016131266 @default.
- W4306913925 cites W2019677361 @default.
- W4306913925 cites W2020331089 @default.
- W4306913925 cites W2020784233 @default.
- W4306913925 cites W2025253353 @default.
- W4306913925 cites W2032077862 @default.
- W4306913925 cites W2041345682 @default.
- W4306913925 cites W2041544510 @default.
- W4306913925 cites W2042816890 @default.
- W4306913925 cites W2046183549 @default.
- W4306913925 cites W2047495447 @default.
- W4306913925 cites W2054960635 @default.
- W4306913925 cites W2055287624 @default.
- W4306913925 cites W2055543630 @default.
- W4306913925 cites W2060004514 @default.
- W4306913925 cites W2069511429 @default.
- W4306913925 cites W2075855311 @default.
- W4306913925 cites W2088402590 @default.
- W4306913925 cites W2096014252 @default.
- W4306913925 cites W2105380856 @default.
- W4306913925 cites W2111668248 @default.
- W4306913925 cites W2118095236 @default.
- W4306913925 cites W2123707618 @default.
- W4306913925 cites W2134362254 @default.
- W4306913925 cites W2138300595 @default.
- W4306913925 cites W2142458597 @default.
- W4306913925 cites W2157535960 @default.
- W4306913925 cites W2157851609 @default.
- W4306913925 cites W2161901483 @default.
- W4306913925 cites W2163031152 @default.
- W4306913925 cites W2166880412 @default.
- W4306913925 cites W2172289055 @default.
- W4306913925 cites W2345012058 @default.
- W4306913925 cites W2469317767 @default.
- W4306913925 cites W2492239722 @default.
- W4306913925 cites W2522993044 @default.
- W4306913925 cites W2526202556 @default.
- W4306913925 cites W2579137335 @default.
- W4306913925 cites W2591667109 @default.
- W4306913925 cites W2597238176 @default.
- W4306913925 cites W2611694282 @default.
- W4306913925 cites W2617205625 @default.
- W4306913925 cites W2758637781 @default.
- W4306913925 cites W2765921352 @default.
- W4306913925 cites W2766044142 @default.
- W4306913925 cites W2771287391 @default.
- W4306913925 cites W2772860165 @default.
- W4306913925 cites W2782075021 @default.
- W4306913925 cites W2795875233 @default.
- W4306913925 cites W2796707256 @default.
- W4306913925 cites W2800226737 @default.
- W4306913925 cites W2802995028 @default.
- W4306913925 cites W2810612816 @default.
- W4306913925 cites W2893427264 @default.
- W4306913925 cites W2905091095 @default.
- W4306913925 cites W2913960606 @default.
- W4306913925 cites W2919896467 @default.
- W4306913925 cites W2950889989 @default.
- W4306913925 cites W2952387488 @default.
- W4306913925 cites W2966261467 @default.
- W4306913925 cites W2994802995 @default.
- W4306913925 cites W3000192795 @default.
- W4306913925 cites W3023609668 @default.
- W4306913925 cites W3025674417 @default.
- W4306913925 cites W3028450214 @default.
- W4306913925 cites W3043593565 @default.
- W4306913925 cites W3097237895 @default.
- W4306913925 cites W3120077678 @default.
- W4306913925 cites W3155199729 @default.
- W4306913925 cites W3165025616 @default.
- W4306913925 cites W3181355369 @default.
- W4306913925 cites W4205605790 @default.
- W4306913925 cites W4205669317 @default.
- W4306913925 cites W4379517865 @default.