{"id":41300,"date":"2025-08-21T18:48:00","date_gmt":"2025-08-21T16:48:00","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/08\/21\/mkln1-dependent-gid4-ctlh-e3-ubiquitin-ligase-complex-assemblies-are-required-to-support-b-cell-antibody-diversification\/"},"modified":"2025-08-21T18:48:00","modified_gmt":"2025-08-21T16:48:00","slug":"mkln1-dependent-gid4-ctlh-e3-ubiquitin-ligase-complex-assemblies-are-required-to-support-b-cell-antibody-diversification","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/08\/21\/mkln1-dependent-gid4-ctlh-e3-ubiquitin-ligase-complex-assemblies-are-required-to-support-b-cell-antibody-diversification\/","title":{"rendered":"MKLN1-dependent GID4\/CTLH E3 ubiquitin ligase complex assemblies are required to support B-cell antibody diversification"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2025 Aug 20:vkaf201. doi: 10.1093\/jimmun\/vkaf201. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>C-terminal to LisH (CTLH) E3 ubiquitin ligase complexes regulate a broad range of biological processes and forms separate supramolecular CTLH-MKLN1 and CTLH-WDR26 assemblies possessing distinct substrate specificities. Our previous work revealed that the CTLH complex utilizes the FAM72A substrate adaptor to ubiquitinate and degrade the uracil-DNA glycosylase 2 (UNG2) base excision repair factor. This outcome in B cells permits deoxyuridine mutations catalyzed by activation-induced cytidine deaminase (AID) to persist toward mutational outcomes and drive antibody diversification events. Here, we report that Mkln1-\/- mice specifically lacking assembly of CTLH-MKLN1 complexes display reduced somatic hypermutation and class switch recombination frequencies due to increased UNG2, similar to Fam72a-\/- mice. Strikingly, Mkln1-\/- mice showed increased germinal center B cells and defects during B-cell development, a phenotype not observed in Fam72a-\/- mice, suggesting that MKLN1 regulates proteins that are independent of FAM72A. Together, this work identifies that CTLH-MKLN1 ubiquitin E3 ligase complexes are critical in generating effective humoral immune responses and reveals distinctions between FAM72A-dependent and -independent CTLH complex modalities.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40838616\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20250821124757&amp;v=2.18.0.post9+e462414\">40838616<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkaf201\">10.1093\/jimmun\/vkaf201<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2025 Aug 20:vkaf201. doi: 10.1093\/jimmun\/vkaf201. Online ahead of print. ABSTRACT C-terminal to LisH (CTLH) E3 ubiquitin ligase complexes regulate a broad range of biological processes and forms separate supramolecular CTLH-MKLN1 and CTLH-WDR26 assemblies possessing distinct substrate specificities. Our previous work revealed that the CTLH complex utilizes the FAM72A substrate adaptor to ubiquitinate and &#8230; <a title=\"MKLN1-dependent GID4\/CTLH E3 ubiquitin ligase complex assemblies are required to support B-cell antibody diversification\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/08\/21\/mkln1-dependent-gid4-ctlh-e3-ubiquitin-ligase-complex-assemblies-are-required-to-support-b-cell-antibody-diversification\/\" aria-label=\"Read more about MKLN1-dependent GID4\/CTLH E3 ubiquitin ligase complex assemblies are required to support B-cell antibody diversification\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[42,71],"tags":[],"class_list":["post-41300","post","type-post","status-publish","format-standard","hentry","category-publicaciones","category-the-journal-of-immunology"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/41300","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=41300"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/41300\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=41300"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=41300"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=41300"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}