title: NF-κB factors control the induction of NFATc1 in B lymphocytes.
abstract: In peripheral lymphocytes, the transcription factors (TFs) NF-κB, NFAT, and AP-1 are the prime targets of signals that emerge from immune receptors. Upon activation, these TFs induce gene networks that orchestrate the growth, expansion, and effector function of peripheral lymphocytes. NFAT and NF-κB factors share several properties, such as a similar mode of induction and architecture in their DNA-binding domain, and there is a subgroup of κB-like DNA promoter motifs that are bound by both types of TFs. However, unlike NFAT and AP-1 factors that interact and collaborate in binding to DNA, NFAT, and NF-κB seem neither to interact nor to collaborate. We show here that NF-κB1/p50 and c-Rel, the most prominent NF-κB proteins in BCR-induced splenic B cells, control the induction of NFATc1/αA, a prominent short NFATc1 isoform. In part, this is mediated through two composite κB/NFAT-binding sites in the inducible Nfatc1 P1 promoter that directs the induction of NFATc1/αA by BCR signals. In concert with coreceptor signals that induce NF-κB factors, BCR signaling induces a persistent generation of NFATc1/αA. These data suggest a tight connection between NFATc1 and NF-κB induction in B lymphocytes contributing to the effector function of peripheral B cells.
authors.affiliation: Department of Molecular Pathology, Institute of Pathology and Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany.
authors.forename: Khalid
authors.initials: K
authors.lastname: Muhammad
authors.forename: Hani
authors.initials: H
authors.lastname: Alrefai
authors.forename: Ralf
authors.initials: R
authors.lastname: Marienfeld
authors.forename: Duong Anh Thuy
authors.initials: DA
authors.lastname: Pham
authors.forename: Krisna
authors.initials: K
authors.lastname: Murti
authors.forename: Amiya K
authors.initials: AK
authors.lastname: Patra
authors.forename: Andris
authors.initials: A
authors.lastname: Avots
authors.forename: Valesca
authors.initials: V
authors.lastname: Bukur
authors.forename: Ugur
authors.initials: U
authors.lastname: Sahin
authors.forename: Eisaku
authors.initials: E
authors.lastname: Kondo
authors.forename: Stefan
authors.initials: S
authors.lastname: Klein-Hessling
authors.forename: Edgar
authors.initials: E
authors.lastname: Serfling
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001665:Binding Sites; D002645:Chickens; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics; D020569:Proto-Oncogene Proteins c-rel / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000235:genetics; D051841:Transcription Factor RelB / Q000235:genetics
chemical_list: D052002:NF-kappa B p50 Subunit; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D020033:Protein Isoforms; D020569:Proto-Oncogene Proteins c-rel; C498144:Rela protein, mouse; C497594:Relb protein, mouse; D051996:Transcription Factor RelA; D051841:Transcription Factor RelB
keywords: Chromatin; Induction; Lymphocytes; NF-κB; Nfatc1 gene; Transcription