NF-kappa B p50/p65 affects the frequency of Ly49 gene expression by NK cells.
In mice, acquisition of Ly49 receptors characterizes one of the developmental stages of NK cells. We previously described a novel Ly49 promoter, Pro1, involved in Ly49 gene regulation in immature NK cells. Pro1 transcriptional activity requires a NF-kappaB binding site; however, only NF-kappaB/p50 binding to this element was observed. Cotransfection of NF-kappaB/p65 with Ly49g Pro1 in LNK cells induced a decrease in the transcriptional activity of the core promoter. Moreover, decreasing NF-kappaB/p65 protein expression by RNA interference increases Pro1 transcriptional activity. A high rate of NF-kappaB/p65 degradation in LNK cells correlates with Pro1 activity, since treatment with the proteasome inhibitor MG132 increased levels of NF-kappaB/p65 protein and decreased Pro1 activity. In addition, analysis of the Ly49 repertoire in NF-kappaB/p50 null mice reveals a decrease in the proportion of NK cells expressing a given Ly49 molecule. The defect in Ly49 expression is observed in the bone marrow and the spleen with a similar altered pattern of developmental stages in each tissue. The frequency of Ly49 expression in NF-kappaB/p52 null mice is slightly increased, indicating the specific role of NF-kappaB/p50 in Ly49 gene activation. These results suggest that NF-kappaB p50/p65 plays a major role in the initiation of Ly49 gene expression in NK cells.
Pascal
Véronique
V
Cancer and Inflammation Program, Laboratory of Experimental Immunology, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD 21702, USA.
Nathan
Neera R
NR
Claudio
Estefania
E
Siebenlist
Ulrich
U
Anderson
Stephen K
SK
D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis* / Q000235:genetics*; D002449:Cell Aggregation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D005787:Gene Frequency / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052002:NF-kappa B p50 Subunit / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D052003:NF-kappa B p52 Subunit / Q000096:biosynthesis / Q000235:genetics; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011401:Promoter Regions, Genetic / Q000276:immunology; D055630:Receptors, NK Cell Lectin-Like; D051996:Transcription Factor RelA / Q000502:physiology*; D015533:Transcriptional Activation / Q000276:immunology
D000950:Antigens, Ly; C527095:Klra7 protein, mouse; D037181:Lectins, C-Type; D052002:NF-kappa B p50 Subunit; D052003:NF-kappa B p52 Subunit; D055650:NK Cell Lectin-Like Receptor Subfamily A; D055630:Receptors, NK Cell Lectin-Like; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; C073701:Nfkb1 protein, mouse; D007371:Interferon-gamma