# NF-κB: A Diverse and Multifunctional Transcription Factor in Holozoans

## TL;DR

This paper reviews the evolution and diverse roles of the NF-κB transcription factor across various holozoan species, including unicellular organisms and early animals.

## Contribution

The paper provides new insights into the conserved and variable functions of NF-κB across holozoans and suggests future research priorities.

## Key findings

- NF-κB and its signaling components are present in a wide range of holozoan taxa.
- The paper highlights conserved and divergent roles of NF-κB in biological processes like pathogen response and development.
- A method for comparing NF-κB dimer structures and their DNA-binding specificities is presented.

## Abstract

Transcription factor nuclear factor-kappa B (NF-κB) and many upstream signaling components have been identified in a diversity of holozoan taxa, including unicellular holozoans (eg Filasterea and Choanoflagellata) and the metazoan phyla Porifera (sponges), Placozoa, and Cnidaria (eg jellyfishes, sea anemones, corals, and hydra). Herein, we review recent progress made toward characterizing the structure, regulation, activity, and biological functions of NF-κB proteins found in these taxa. We also provide an updated phylogenetic sampling of NF-κB orthologs highlighting their different domain configurations among holozoans, as well as a method for comparing the computationally predicted three-dimensional structures of NF-κB dimers and relating these structures to their amino acid similarities and DNA-binding specificities. This synthesis reveals new insights regarding the evolutionarily conserved and variable domain-dependent activities and regulation of holozoan NF-κBs. Further, we provide an overview of the roles of NF-κB in pathogen responses, stress responses, symbiosis, and development, with a focus on recent findings from sponges and cnidarians. This curation of a growing body of knowledge highlights both conserved and divergent roles of NF-κB in foundational biological processes. Finally, we suggest priorities for future research on the evolution of NF-κB structure and function. Overall, investigations of NF-κB in diverse holozoan taxa will continue to provide information about the origins of this important and pervasive transcriptional regulator and will also contribute to an understanding of the responses of sentinel species to the modern-day stresses associated with changing environmental conditions and novel pathogen-based diseases.