¹INSERM U542, Université Paris-Sud, Hôpital Paul Brousse, Villejuif, France

Correspondence: Dr A Vazquez, INSERM U542, Université Paris-Sud, Hôpital Paul Brousse, Batiment, Lavoisier, 14 Avenue Paul Vaillant Couturier, Villejuif Cedex, Val de Marne 94807, France. E-mail: vazquez@vjf.inserm.fr

²These authors contributed equally to this work.

Received 31 August 2007; Revised 12 November 2007; Accepted 3 December 2007; Published online 14 January 2008.

Abstract

In this study, we showed that the transforming growth factor (TGF)-mediated apoptosis of Burkitt's lymphoma BL41 cells is dependent on the BH3-only protein Bim. In contrast to what has been observed with other cell types, TGF activation did not promote Bim upregulation in BL41 cells, but instead resulted in Bim release from the mitochondria. Indeed, Bim levels were high in healthy BL41 cells, in which they dimerized with the Bcl-2-like protein Mcl-1 at the mitochondrial surface. In healthy and TGF-activated BL41 cells, unlike in epithelial cells or hepatocytes, Bim did not associate with Bcl-2 or Bcl-xL. TGF activation of BL41 cells triggered the p38-dependent activation of caspase-8, causing the cleavage of Mcl-1 and the transfer of Bim from the mitochondria to the cytoskeleton. In addition to mitochondrial activation, this relocation of Bim may facilitate the complete demise of a cell death that is beyond the commitment point to apoptosis and may represent a hallmark of the TGF-mediated apoptosis of human lymphoma B cells.