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

Area of Science:

• Evolutionary Biology
• Molecular Biology
• Immunology

Background:

• The transcription factor nuclear factor-kappa B (NF-κB) and its signaling pathway are crucial in immunity and development.
• NF-κB components are present in a wide range of holozoan taxa, including unicellular organisms and early-branching metazoans like sponges and cnidarians.
• Understanding NF-κB evolution provides insights into the origins of complex biological processes.

Purpose of the Study:

• To review recent advancements in characterizing the structure, regulation, activity, and biological functions of NF-κB proteins in diverse holozoan taxa.
• To present an updated phylogenetic analysis of NF-κB orthologs and a method for comparing predicted 3D structures and DNA-binding specificities.
• To synthesize current knowledge on conserved and divergent roles of NF-κB in foundational biological processes and its involvement in responses to environmental changes.

Main Methods:

• Review of recent scientific literature on NF-κB in holozoan taxa.
• Phylogenetic analysis of NF-κB orthologs to determine domain configurations.
• Computational prediction and comparison of three-dimensional structures of NF-κB dimers.

Main Results:

• NF-κB proteins and signaling components are conserved across unicellular holozoans, sponges, placozoans, and cnidarians.
• Analysis reveals conserved and variable domain-dependent activities and regulation of holozoan NF-κBs.
• NF-κB plays significant roles in pathogen and stress responses, symbiosis, and development in sponges and cnidarians.

Conclusions:

• NF-κB is an evolutionarily ancient transcriptional regulator with conserved and divergent roles in fundamental biological processes across holozoans.
• Investigating NF-κB in diverse holozoans offers insights into the origins of this regulator and the adaptive responses of organisms to environmental stressors.
• Future research should prioritize understanding the evolution of NF-κB structure and function to address its role in modern environmental challenges.