{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T18:40:19Z","timestamp":1792608019761,"version":"4.5.0"},"reference-count":80,"publisher":"American Society for Clinical Investigation","issue":"20","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,22]]},"abstract":"<jats:p>\n                    Ubiquitination is an important posttranslational modification associated with essential cellular processes. Here we show that deletion of E3 ubiquitin ligase HECTD3 \u2014 germline or in hematopoietic compartment, including in Cd11c\n                    <jats:sup>+<\/jats:sup>\n                    cells \u2014 causes severe disease and increased production of proinflammatory cytokines in a murine model of ulcerative colitis (UC). HECTD3 mRNA levels were found reduced in colonic tissues of patients with UC, which highlights a potential role for HECTD3 in regulating inflammatory responses in UC. We identified MyD88, a central adaptor in the TLR\/IL-1R signaling and inflammatory response, as a target for HECTD3 ubiquitination. We demonstrate that HECTD3 ubiquitinates MyD88 through K27-linked Poly-Ub chains in a nondegradative manner. HECTD3-KO GM-CSF\u2013bone marrow\u2013derived cells treated with the TLR4 ligand LPS produced more proinflammatory cytokines, showed elevated phosphorylation of NF-\u03baB and IRAK4, as well as increased association of MyD88 with IRAK4, demonstrating that HECTD3 controls MyD88\/IRAK4\/NF-\u03baB axis. Inhibition of MyD88 activity rescued colitis severity in the HECTD3-KO mice, including the elevated proinflammatory cytokine production. Thus, our results establish MyD88 as a target for HECTD3 nondegradative polyubiquitination and restriction of innate immune colonic inflammation.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.185437","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:01:11Z","timestamp":1790265671000},"source":"Crossref","is-referenced-by-count":0,"title":["The E3 ubiquitin ligase HECTD3 controls immune colonic inflammation by restricting MyD88 activation and signaling"],"prefix":"10.1172","volume":"11","author":[{"given":"Shamima","family":"Islam","sequence":"first","affiliation":[{"name":"Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahnewaj","family":"Mannan","sequence":"additional","affiliation":[{"name":"Department of Immunology, H. 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