1. Cross-species analysis reveals evolving and conserved features of the nuclear factor κB (NF-κB) proteins.
- Author
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Ryzhakov G, Teixeira A, Saliba D, Blazek K, Muta T, Ragoussis J, and Udalova IA
- Subjects
- Animals, B-Cell Lymphoma 3 Protein, Humans, Nuclear Localization Signals genetics, Nuclear Localization Signals metabolism, Protein Multimerization physiology, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins metabolism, Species Specificity, Transcription Factors genetics, Transcription Factors metabolism, Biological Evolution, NF-kappa B genetics, NF-kappa B metabolism, Sea Anemones genetics, Sea Anemones metabolism
- 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.
- Published
- 2013
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