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

作者: Johan Garaude , Seyma Cherni , Sandra Kaminski , Etienne Delepine , Christine Chable-Bessia

DOI: 10.4049/JIMMUNOL.177.11.7607

关键词:

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

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