ERK5 activates NF-kappaB in leukemic T cells and is essential for their growth in vivo

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 lev...

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Published inThe Journal of immunology (1950) 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
LanguageEnglish
Published United States Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists 01.12.2006
Subjects
Animals
Apoptosis - physiology
Biochemistry, Molecular Biology
Blotting, Western
Cell Proliferation
eIF-2 Kinase - metabolism
Electrophoresis, Polyacrylamide Gel
Humans
Immunoprecipitation
Jurkat Cells
Leukemia - enzymology
Life Sciences
Lymphocyte Activation - immunology
Mice
Mitogen-Activated Protein Kinase 7 - metabolism
NF-kappa B - metabolism
Protein Transport - immunology
RNA, Small Interfering
T-Lymphocytes - metabolism
Transcriptional Activation
Transfection
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Summary: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-kappaB 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.
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ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.177.11.7607