PT  - JOURNAL ARTICLE
AU  - Leah M. Williams
AU  - Melissa M. Inge
AU  - Katelyn M. Mansfield
AU  - Anna Rasmussen
AU  - Jamie Afghani
AU  - Mikhail Agrba
AU  - Colleen Albert
AU  - Cecilia Andersson
AU  - Milad Babaei
AU  - Mohammad Babaei
AU  - Abigail Bagdasaryants
AU  - Arianna Bonilla
AU  - Amanda Browne
AU  - Sheldon Carpenter
AU  - Tiffany Chen
AU  - Blake Christie
AU  - Andrew Cyr
AU  - Katie Dam
AU  - Nicholas Dulock
AU  - Galbadrakh Erdene
AU  - Lindsie Esau
AU  - Stephanie Esonwune
AU  - Anvita Hanchate
AU  - Xinli Huang
AU  - Timothy Jennings
AU  - Aarti Kasabwala
AU  - Leanne Kehoe
AU  - Ryan Kobayashi
AU  - Migi Lee
AU  - Andre LeVan
AU  - Yuekun Liu
AU  - Emily Murphy
AU  - Avanti Nambiar
AU  - Meagan Olive
AU  - Devansh Patel
AU  - Flaminio Pavesi
AU  - Christopher A. Petty
AU  - Yelena Samofalova
AU  - Selma Sanchez
AU  - Camilla Stejskal
AU  - Yinian Tang
AU  - Alia Yapo
AU  - John P. Cleary
AU  - Sarah A. Yunes
AU  - Trevor Siggers
AU  - Thomas D. Gilmore
TI  - Transcription factor NF-κB in a basal metazoan, the sponge, has conserved and unique sequences, activities, and regulation
AID  - 10.1101/691097
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 691097
4099  - http://biorxiv.org/content/early/2019/07/12/691097.short
4100  - http://biorxiv.org/content/early/2019/07/12/691097.full
AB  - Biological and biochemical functions of immunity transcription factor NF-κB in basal metazoans are largely unknown. Herein, we characterize transcription factor NF-κB from the demosponge Amphimedon queenslandica (Aq), in the phylum Porifera. Structurally and phylogenetically, the Aq-NF-κB protein is most similar to NF-κB p100 and p105 among vertebrate proteins, with an N-terminal DNA-binding/dimerization domain, a C-terminal Ankyrin (ANK) repeat domain, and a DNA binding-site profile more similar to human NF-κB proteins than Rel proteins. Aq-NF-κB also resembles the mammalian NF-κB protein p100 in that C-terminal truncation results in translocation of Aq-NF-κB to the nucleus and increases its transcriptional activation activity. Overexpression of a human or sea anemone IκB kinase (IKK) can induce C-terminal processing of Aq-NF-κB in vivo, and this processing requires C-terminal serine residues in Aq-NF-κB. Unlike human NF-κB p100, however, the C-terminal sequences of Aq-NF-κB do not effectively inhibit its DNA-binding activity when expressed in human cells. Tissue of another demosponge, a black encrusting sponge, contains NF-κB site DNA-binding activity and an NF-κB protein that appears mostly processed and in the nucleus of cells. NF-κB DNA-binding activity and processing is increased by treatment of sponge tissue with LPS. By transcriptomic analysis of A. queenslandica we identified likely homologs to many upstream NF-κB pathway components. These results present a functional characterization of the most ancient metazoan NF-κB protein to date, and show that many characteristics of mammalian NF-κB are conserved in sponge NF-κB, but the mechanism by which NF-κB functions and is regulated in the sponge may be somewhat different.