title: Cross-species analysis reveals evolving and conserved features of the nuclear factor κB (NF-κB) proteins.
abstract: NF-κB is a key regulator of immune gene expression in metazoans. It is currently unclear what changes occurred in NF-κB during animal evolution and what features remained conserved. To address this question, we compared the biochemical and functional properties of NF-κB proteins derived from human and the starlet sea anemone (Nematostella vectensis) in 1) a high-throughput assay of in vitro preferences for DNA sequences, 2) ChIP analysis of in vivo recruitment to the promoters of target genes, 3) a LUMIER-assisted examination of interactions with cofactors, and 4) a transactivation assay. We observed a remarkable evolutionary conservation of the DNA binding preferences of the animal NF-κB orthologs. We also show that NF-κB dimerization properties, nuclear localization signals, and binding to cytosolic IκBs are conserved. Surprisingly, the Bcl3-type nuclear IκB proteins functionally pair up only with NF-κB derived from their own species. The basis of the differential NF-κB recognition by IκB subfamilies is discussed.
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, London W6 8LH, United Kingdom. grigory@ryzhakov.co.uk
authors.forename: Grigory
authors.initials: G
authors.lastname: Ryzhakov
authors.forename: Ana
authors.initials: A
authors.lastname: Teixeira
authors.forename: David
authors.initials: D
authors.lastname: Saliba
authors.forename: Katrina
authors.initials: K
authors.lastname: Blazek
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Muta
authors.forename: Jiannis
authors.initials: J
authors.lastname: Ragoussis
authors.forename: Irina A
authors.initials: IA
authors.lastname: Udalova
mesh_terms: D000818:Animals; D000081242:B-Cell Lymphoma 3 Protein; D005075:Biological Evolution; D006801:Humans; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism*; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012615:Sea Anemones / Q000235:genetics* / Q000378:metabolism*; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D016328:NF-kappa B; D019913:Nuclear Localization Signals; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors