PeproTech Inc.
Originally published online as doi:10.1189/jlb.0508287 on September 11, 2008

Published online before print September 11, 2008
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jlb.0508287v1
84/6/1604    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Najjar, I.
Right arrow Articles by Fagard, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Najjar, I.
Right arrow Articles by Fagard, R.
(Journal of Leukocyte Biology. 2008;84:1604-1612.)
© 2008 by Society for Leukocyte Biology

Novel function of STAT1β in B cells: induction of cell death by a mechanism different from that of STAT1{alpha}

Imen Najjar*,1, Pierre Olivier Schischmanoff*, Fanny Baran-Marszak*, Pierre-Antoine Deglesne*, Ibtissam Youlyouz-Marfak{dagger}, Mathieu Pampin{ddagger}, Jean Feuillard{dagger}, Georg W. Bornkamm§, Mounira K. Chelbi-Alix{ddagger} and Remi Fagard*,2

* Université Paris 13, EA 3406, Service de biochimie, APHP, Hôpital Avicenne, Cedex, France;
{ddagger} CNRS FRE 2937, Institut Lwoff, Villejuif, France;
{dagger} Unité Mixte de Recherche (UMR), Centre National de la Recherche Scientifique (CNRS) 6101, and Laboratoire d’Hématologie, Centre Hospitalier Universitaire (CHU) Dupuytren and Faculté de Médecine, Université de Limoges, France; and
§ Forschungszentrum für Umwelt und Gesundheit (GSF), Institute of Clinical Molecular Biology and Tumor Genetics, Munich, Germany

2 Correspondence: Service de biochimie, Hôpital Avicenne, 125 route de Stalingrad, 93009 Bobigny Cedex, France. E-mail: remi.fagard{at}avc.aphp.fr

Alternate splicing of STAT1 produces two isoforms: {alpha}, known as the active form, and β, previously shown to act as a dominant-negative factor. Most studies have dealt with STAT1{alpha}, showing its involvement in cell growth control and cell death. To examine the specific function of either isoform in cell death, a naturally STAT1-deficient human B cell line was transfected to express STAT1{alpha} or STAT1β. STAT1{alpha}, expressed alone, enhanced cell death, potentiated the fludarabine-induced apoptosis, and enhanced the nuclear location, the phosphorylation, and the transcriptional activity of p53. Unexpectedly, STAT1β, expressed alone, induced cell death through a mechanism that was independent of the nuclear function of p53. Indeed, in STAT1β-expressing B cells, p53 was stricktly cytoplasmic where it formed clusters, and there was no induction of the transcriptional activity of p53. These data reveal a novel role of STAT1β in programmed cell death, which is independent of p53.

Key Words: B lymphocytes • p53 • fludarabine