{"id":41387,"date":"2025-08-24T23:47:51","date_gmt":"2025-08-24T21:47:51","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/08\/24\/rack1-is-required-for-normal-b-cell-development-and-signaling-but-not-rag1-degradation\/"},"modified":"2025-08-24T23:47:51","modified_gmt":"2025-08-24T21:47:51","slug":"rack1-is-required-for-normal-b-cell-development-and-signaling-but-not-rag1-degradation","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/08\/24\/rack1-is-required-for-normal-b-cell-development-and-signaling-but-not-rag1-degradation\/","title":{"rendered":"RACK1 is required for normal B cell development and signaling but not RAG1 degradation"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2025 Aug 24:vkaf217. doi: 10.1093\/jimmun\/vkaf217. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>V(D)J recombination is constrained by timely degradation of the RAG1 and RAG2 proteins through distinct mechanisms. Previously, we showed that full-length RAG1 stability is regulated by viral protein R binding protein (VprBP) through its association with an amino-terminal region in RAG1, but the mechanism remains unclear. As an unbiased approach to uncover potential cofactors involved in the process, we compared protein interactomes between RAG1\/RAG2 complexes formed when the amino-terminal third of RAG1 was present or absent. These experiments identified RACK1 as preferentially associating with full-length RAG1. Because RACK1 is implicated in mediating protein degradation in other contexts, we evaluated how loss of RACK1 in B cells affects B cell development and V(D)J recombination. We find that conditional disruption of Rack1 expression in the B lineage in mice blocks B cell development at the pro-B cell stage and impairs V(D)J recombination after Igh DH-JH rearrangement. In this background, enforced Bcl2 expression does not significantly rescue B cell development but does enable the V(D)J recombination defect to be bypassed. However, the phenotype of these mice does not show the excessive Igk rearrangement, skewing toward Ig\u03bb+ B cells, or increased RAG1 protein levels observed when VprBP expression is similarly disrupted in B cells, arguing against RACK1 serving as a cofactor in RAG1 degradation. Further studies provide evidence that loss of RACK1 in primary B cells dysregulates cell cycle progression, apoptosis, proliferation, and signaling through MAPK and NF-\u03baB pathways.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40849887\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20250824174748&amp;v=2.18.0.post9+e462414\">40849887<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkaf217\">10.1093\/jimmun\/vkaf217<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2025 Aug 24:vkaf217. doi: 10.1093\/jimmun\/vkaf217. Online ahead of print. ABSTRACT V(D)J recombination is constrained by timely degradation of the RAG1 and RAG2 proteins through distinct mechanisms. Previously, we showed that full-length RAG1 stability is regulated by viral protein R binding protein (VprBP) through its association with an amino-terminal region in RAG1, but the &#8230; <a title=\"RACK1 is required for normal B cell development and signaling but not RAG1 degradation\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/08\/24\/rack1-is-required-for-normal-b-cell-development-and-signaling-but-not-rag1-degradation\/\" aria-label=\"Read more about RACK1 is required for normal B cell development and signaling but not RAG1 degradation\">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-41387","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\/41387","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=41387"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/41387\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=41387"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=41387"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=41387"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}