RT Journal Article
SR Electronic
T1 Transcription factor NF-κB in a basal metazoan, the sponge, has conserved and unique sequences, activities, and regulation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 691097
DO 10.1101/691097
A1 Leah M. Williams
A1 Melissa M. Inge
A1 Katelyn M. Mansfield
A1 Anna Rasmussen
A1 Jamie Afghani
A1 Mikhail Agrba
A1 Colleen Albert
A1 Cecilia Andersson
A1 Milad Babaei
A1 Mohammad Babaei
A1 Abigail Bagdasaryants
A1 Arianna Bonilla
A1 Amanda Browne
A1 Sheldon Carpenter
A1 Tiffany Chen
A1 Blake Christie
A1 Andrew Cyr
A1 Katie Dam
A1 Nicholas Dulock
A1 Galbadrakh Erdene
A1 Lindsie Esau
A1 Stephanie Esonwune
A1 Anvita Hanchate
A1 Xinli Huang
A1 Timothy Jennings
A1 Aarti Kasabwala
A1 Leanne Kehoe
A1 Ryan Kobayashi
A1 Migi Lee
A1 Andre LeVan
A1 Yuekun Liu
A1 Emily Murphy
A1 Avanti Nambiar
A1 Meagan Olive
A1 Devansh Patel
A1 Flaminio Pavesi
A1 Christopher A. Petty
A1 Yelena Samofalova
A1 Selma Sanchez
A1 Camilla Stejskal
A1 Yinian Tang
A1 Alia Yapo
A1 John P. Cleary
A1 Sarah A. Yunes
A1 Trevor Siggers
A1 Thomas D. Gilmore
YR 2019
UL http://biorxiv.org/content/early/2019/07/12/691097.abstract
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.