Looking Down on NF-κB

ABSTRACT

The diversified NF-κB transcription factor family has been extensively characterized in organisms ranging from flies to humans. However, homologs of NF-κB and many upstream signaling components have recently been characterized in basal phyla, including Cnidaria (sea anemones, corals, hydras, and jellyfish), Porifera (sponges), and single-celled protists, including Capsaspora owczarzaki and some choanoflagellates. Herein, we review what is known about basal NF-κBs and how that knowledge informs on the evolution and conservation of key sequences and domains in NF-κB, as well as the regulation of NF-κB activity. The structures and DNA-binding activities of basal NF-κB proteins resemble those of mammalian NF-κB p100 proteins, and their posttranslational activation appears to have aspects of both canonical and noncanonical pathways in mammals. Several studies suggest that the single NF-κB proteins found in some basal organisms have dual roles in development and immunity. Further research on NF-κB in invertebrates will reveal information about the evolutionary roots of this major signaling pathway, will shed light on the origins of regulated innate immunity, and may have relevance to our understanding of the responses of ecologically important organisms to changing environmental conditions and emerging pathogen-based diseases.

KEYWORDS:

• NF-kappaB
• development
• evolution
• innate immunity
• signal transduction

SUPPLEMENTAL MATERIAL

Supplemental material is available online only.

ACKNOWLEDGMENTS

We thank Anvitha Addanki for help with the analysis of choanoflagellate NF-κB proteins.

Our research on the evolution and basal functions of NF-κB was supported by the following National Science Foundation grants (to T.D.G.): MCB-0924749, IOS-1557804, and IOS-1937650. L.M.W. was supported by an NSF Graduate Research Fellowship.

We declare no conflict of interest.

Additional information

Notes on contributors

Leah M. Williams

Leah M. Williams is a Ph.D. candidate in cell and molecular biology at Boston University (BU). She received her bachelor of arts from Wheaton College (Massachusetts) and then worked for 2 years at Harvard Medical School doing proteomic pathway discovery before starting her graduate career. Ms. Williams’s doctoral research seeks to understand immunity in evolutionarily distant and ecologically significant organisms, and she has published seminal papers on basal immunity in sponges and cnidarians. Her research has been supported by multiple internal BU grants and external grants, including an NSF GRFP. Ms. Williams has been a mentor for a dozen undergraduate and high school students, including NSF-REU students, and she has served on panels for science fairs and volunteered in various scientific teaching settings for students in K-12 through college. Ms. Williams intends to pursue postdoctoral research combining molecular and systems approaches to answer evolutionary and ecological questions.

Thomas D. Gilmore

Thomas D. Gilmore is a professor of biology at Boston University (BU). He received his Ph.D. from the University of California, Berkeley, performed postdoctoral research at the University of Wisconsin, and has been on the faculty at BU since 1987. Dr. Gilmore’s lab has made key contributions to many aspects of NF-κB biology, starting with his postdoctoral studies on the v-Rel oncoprotein with Howard Temin. Dr. Gilmore lab’s longstanding research interest has been in the area of NF-κB signaling and diseases, including human B-cell diseases, and disease pathologies of marine invertebrates, such as corals and sea anemones. This research has been supported by grants from the NIH, NSF, and the American Cancer Society, among others. Dr. Gilmore has written numerous reviews on NF-κB, and his lab hosts the website nf-kb.org. Dr. Gilmore has carried out research primarily with an army of student trainees, including 27 Ph.D. students, 41 M.A. students, and over 100 undergraduates. Dr. Gilmore has received BU’s highest awards for teaching and research.