Clybouw C, Mchichi B E L, Hadji A, Portier A, Auffredou M T, Arnoult D, Leca G, Vazquez A
INSERM U542, Université Paris-Sud, Hôpital Paul Brousse, Villejuif, France.
Oncogene. 2008 May 29;27(24):3446-56. doi: 10.1038/sj.onc.1211009. Epub 2008 Jan 14.
In this study, we showed that the transforming growth factor beta (TGFbeta)-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, TGFbeta 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 TGFbeta-activated BL41 cells, unlike in epithelial cells or hepatocytes, Bim did not associate with Bcl-2 or Bcl-xL. TGFbeta 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 TGFbeta-mediated apoptosis of human lymphoma B cells.
在本研究中，我们发现转化生长因子β（TGFβ）介导的伯基特淋巴瘤BL41细胞凋亡依赖于仅含BH3结构域的蛋白Bim。与在其他细胞类型中观察到的情况相反，TGFβ激活并未促进BL41细胞中Bim的上调，而是导致Bim从线粒体释放。实际上，健康的BL41细胞中Bim水平很高，在这些细胞中它在线粒体表面与Bcl-2样蛋白Mcl-1二聚化。在健康和TGFβ激活的BL41细胞中，与上皮细胞或肝细胞不同，Bim不与Bcl-2或Bcl-xL结合。BL41细胞的TGFβ激活触发了依赖p38的caspase-8激活，导致Mcl-1的裂解以及Bim从线粒体转移至细胞骨架。除了线粒体激活外，Bim的这种重新定位可能有助于细胞死亡的彻底发生，这种细胞死亡超出了凋亡的起始点，可能代表了TGFβ介导的人类淋巴瘤B细胞凋亡的一个标志。
