FOXO3-NF-kappaB RelA Protein Complexes Reduce Proinflammatory Cell Signaling and Function Journal Article

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Authors: Thompson, M. G.; Larson, M.; Vidrine, A.; Barrios, K.; Navarro, F.; Meyers, K.; Simms, P; Prajapati, K; Chitsike, L; Hellman, L. M.; Baker, B. M.; Watkins, S. K.
Article Title: FOXO3-NF-kappaB RelA Protein Complexes Reduce Proinflammatory Cell Signaling and Function
Abstract: Tumor-associated myeloid cells, including dendritic cells (DCs) and macrophages, are immune suppressive. This study demonstrates a novel mechanism involving FOXO3 and NF-kappaB RelA that controls myeloid cell signaling and impacts their immune-suppressive nature. We find that FOXO3 binds NF-kappaB RelA in the cytosol, impacting both proteins by preventing FOXO3 degradation and preventing NF-kappaB RelA nuclear translocation. The location of protein-protein interaction was determined to be near the FOXO3 transactivation domain. In turn, NF-kappaB RelA activation was restored upon deletion of the same sequence in FOXO3 containing the DNA binding domain. We have identified for the first time, to our knowledge, a direct protein-protein interaction between FOXO3 and NF-kappaB RelA in tumor-associated DCs. These detailed biochemical interactions provide the foundation for future studies to use the FOXO3-NF-kappaB RelA interaction as a target to enhance tumor-associated DC function to support or enhance antitumor immunity.
Journal Title: Journal of immunology (Baltimore, Md.: 1950)
Volume: 195
Issue: 12
ISSN: 1550-6606; 0022-1767
Publisher: by The American Association of Immunologists, Inc  
Journal Place: United States
Date Published: 2015
Start Page: 5637
End Page: 5647
Language: eng
DOI/URL:

10.4049/jimmunol.1501758
Notes: LR: 20151214; CI: Copyright (c) 2015; GR: GM06079/GM/NIGMS NIH HHS/United States; GR: R00 CA151294/CA/NCI NIH HHS/United States; GR: R00CA151294/CA/NCI NIH HHS/United States; JID: 2985117R; NIHMS732894; OID: NLM: NIHMS732894; OID: NLM: PMC4670825; 2015/08/04 [received]; 2015/10/16 [accepted]; 2015/11/11 [aheadofprint]; ppublish