ERK5 Activates NF-κB in Leukemic T Cells and Is Essential for Their Growth In Vivo

• Published in: Journal of Immunology Vol. 177; no. 11; pp. 7607 - 7617
• Main Authors: Garaude, Johan, Cherni, Seyma, Kaminski, Sandra, Delepine, Etienne, Chable-Bessia, Christine, Benkirane, Monsef, Borges, Joana, Pandiella, Atanasio, Iñiguez, Miguel Angel, Fresno, Manuel, Hipskind, Robert A., Villalba, Martin
• Format: Journal Article
• Language: English
• Published: 01.12.2006
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.177.11.7607

Abstract MAPK cascades play a central role in the cellular response to the environment. The pathway involving the MAPK ERK5 mediates growth factor- and stress-induced intracellular signaling that controls proliferation or survival depending upon the cell context. In this study, we show that reducing ERK5 levels with a specific small hairpin RNA 5 (shERK5) reduced cell viability, sensitized cells to death receptor-induced apoptosis, and blocked the palliative effects of phorbol ester in anti-Fas Ab-treated cells. shERK5 decreased nuclear accumulation of the NF-κB p65 subunit, and conversely, ectopic activation of ERK5 led to constitutive nuclear localization of p65 and increased its ability to trans activate specific reporter genes. Finally, the T lymphoma cell line EL-4, upon expression of shERK5, proliferated in vitro, but failed to induce s.c. tumors in mice. Our results suggest that ERK5 is essential for survival of leukemic T cells in vivo, and thus represents a promising target for therapeutic intervention in this type of malignancy.