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- W2912343713 abstract "Abstract Polyubiquitination promotes proteasomal degradation, or signaling and localization, of targeted proteins. Here we show that the E3 ubiquitin ligase Hectd3 is necessary for pathogenic Th17 cell generation in experimental autoimmune encephalomyelitis (EAE), a mouse model for human multiple sclerosis. Hectd3-deficient mice have lower EAE severity, reduced Th17 program and inefficient Th17 cell differentiation. However, Stat3, but not RORγt, has decreased polyubiquitination, as well as diminished tyrosine-705 activating phosphorylation. Additionally, non-degradative polyubiquitination of Malt1, critical for NF-κB activation and Th17 cell function, is reduced. Mechanistically, Hectd3 promotes K27-linked and K29-linked polyubiquitin chains on Malt1, and K27-linked polyubiquitin chains on Stat3. Moreover, Stat3 K180 and Malt1 K648 are targeted by Hectd3 for non-degradative polyubiquitination to mediate robust generation of RORγt + IL-17A hi effector CD4 + T cells. Thus, our studies delineate a mechanism connecting signaling related polyubiquitination of Malt1 and Stat3, leading to NF-kB activation and RORγt expression, to pathogenic Th17 cell function in EAE." @default.
- W2912343713 created "2019-02-21" @default.
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- W2912343713 date "2019-02-11" @default.
- W2912343713 modified "2023-10-16" @default.
- W2912343713 title "Hectd3 promotes pathogenic Th17 lineage through Stat3 activation and Malt1 signaling in neuroinflammation" @default.
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- W2912343713 cites W1754164368 @default.
- W2912343713 cites W1887207058 @default.
- W2912343713 cites W1900297117 @default.
- W2912343713 cites W1973603971 @default.
- W2912343713 cites W1982926364 @default.
- W2912343713 cites W1987628377 @default.
- W2912343713 cites W1995110654 @default.
- W2912343713 cites W1998000193 @default.
- W2912343713 cites W1998895238 @default.
- W2912343713 cites W2000750335 @default.
- W2912343713 cites W2006249161 @default.
- W2912343713 cites W2012082059 @default.
- W2912343713 cites W2014750930 @default.
- W2912343713 cites W2015347941 @default.
- W2912343713 cites W2021340905 @default.
- W2912343713 cites W2024107692 @default.
- W2912343713 cites W2030674514 @default.
- W2912343713 cites W2032030313 @default.
- W2912343713 cites W2034599968 @default.
- W2912343713 cites W2036012609 @default.
- W2912343713 cites W2039096179 @default.
- W2912343713 cites W2047677831 @default.
- W2912343713 cites W2062577468 @default.
- W2912343713 cites W2066558593 @default.
- W2912343713 cites W2068671129 @default.
- W2912343713 cites W2070873221 @default.
- W2912343713 cites W2084388036 @default.
- W2912343713 cites W2085685430 @default.
- W2912343713 cites W2087240015 @default.
- W2912343713 cites W2091420542 @default.
- W2912343713 cites W2092002465 @default.
- W2912343713 cites W2107797460 @default.
- W2912343713 cites W2113561458 @default.
- W2912343713 cites W2116828514 @default.
- W2912343713 cites W2122082443 @default.
- W2912343713 cites W2122939321 @default.
- W2912343713 cites W2133459528 @default.
- W2912343713 cites W2133737057 @default.
- W2912343713 cites W2138141169 @default.
- W2912343713 cites W2142017607 @default.
- W2912343713 cites W2142057312 @default.
- W2912343713 cites W2143916173 @default.
- W2912343713 cites W2147549827 @default.
- W2912343713 cites W2156177776 @default.
- W2912343713 cites W2157837362 @default.
- W2912343713 cites W2159252214 @default.
- W2912343713 cites W2171230450 @default.
- W2912343713 cites W2171232688 @default.
- W2912343713 cites W2178012989 @default.
- W2912343713 cites W2178194641 @default.
- W2912343713 cites W2187949237 @default.
- W2912343713 cites W2196731768 @default.
- W2912343713 cites W2219188266 @default.
- W2912343713 cites W2257747161 @default.
- W2912343713 cites W2308917818 @default.
- W2912343713 cites W2310322011 @default.
- W2912343713 cites W2338409690 @default.
- W2912343713 cites W2463936901 @default.
- W2912343713 cites W2480860498 @default.
- W2912343713 cites W2578139436 @default.
- W2912343713 cites W2614308430 @default.
- W2912343713 cites W2734356004 @default.
- W2912343713 cites W2766922625 @default.
- W2912343713 cites W2776663677 @default.
- W2912343713 cites W2808957738 @default.
- W2912343713 cites W2809163557 @default.
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- W2912343713 doi "https://doi.org/10.1038/s41467-019-08605-3" @default.
- W2912343713 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6370850" @default.