{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:58:55Z","timestamp":1790917135405,"version":"4.1.0"},"reference-count":54,"publisher":"Rockefeller University Press","issue":"7","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1998,4,6]]},"abstract":"<jats:p>The polypeptide (p)50 molecule, a subunit of nuclear factor (NF)-\u03baB, is produced after proteolytic processing of the p105 precursor (NF-\u03baB1). Although the p105 precursor has been postulated to play a role in the regulation of the Rel\/NF-\u03baB activity, its physiological relevance remains unclear. To investigate that, we generated mutant mice lacking the COOH terminal half of the p105 precursor, but expressing the p50 product (p105\u2212\/\u2212). These mutant mice displayed an inflammatory phenotype composed of lymphocytic infiltration in lungs and liver, and an increased susceptibility to opportunistic infections. Enlargement of multiple lymph nodes, splenomegaly due to erythrocytic extramedullary hematopoiesis, and lymphoid hyperplasia were also observed in p105\u2212\/\u2212 mice. Cytokine production in p105\u2212\/\u2212 macrophages was severely impaired, whereas proliferative responses of p105\u2212\/\u2212 B cells were increased. T cell functions were only moderately impaired in mutant mice. Loss of p105 also led to enhanced constitutive p50 homodimer and inducible NF-\u03baB activities in unstimulated and stimulated cells, respectively. As several genes regulated by Rel\/NF-\u03baB were upregulated in p105\u2212\/\u2212 thymus but downregulated in p105\u2212\/\u2212 macrophages, the enhanced p50 homodimers appear to function as transcriptional activators or repressors, depending on the cell type. Thus, the p105 precursor is indispensable in the control of p50 activity, and lack of the precursor has distinct effects on different cells.<\/jats:p>","DOI":"10.1084\/jem.187.7.985","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:49:30Z","timestamp":1027702170000},"page":"985-996","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":121,"title":["Chronic Inflammation and Susceptibility to Bacterial Infections in Mice Lacking the Polypeptide (p)105 Precursor (NF-\u03baB1) but Expressing p50"],"prefix":"10.1084","volume":"187","author":[{"given":"Hideaki","family":"Ishikawa","sequence":"first","affiliation":[{"name":"From *the Department of Oncology, and \u2021the Department of Experimental Pathology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estefania","family":"Claudio","sequence":"additional","affiliation":[{"name":"From *the Department of Oncology, and \u2021the Department of Experimental Pathology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Dambach","sequence":"additional","affiliation":[{"name":"From *the Department of Oncology, and \u2021the Department of Experimental Pathology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Ravent\u00f3s-Su\u00e1rez","sequence":"additional","affiliation":[{"name":"From *the Department of Oncology, and \u2021the Department of Experimental Pathology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 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