Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
FEBS Lett. 2012 Mar 23;586(6):747-52. doi: 10.1016/j.febslet.2012.01.034. Epub 2012 Jan 26.
Scythe is a nuclear protein that has been implicated in the apoptotic process in Drosophila melanogaster; however, its role in apoptosis of mammalian cells is not fully elucidated. Here we show that cleavage of Scythe by caspase-3 occurs after activation of both the extrinsic (i.e. Fas/APO-1-mediated) and the intrinsic (i.e. staurosporine-induced) apoptosis pathway. Moreover, this caspase-dependent cleavage correlates with Scythe translocation from the nucleus to the cytosol. We also show that cytosolic re-localization of Scythe is required for Fas/APO-1-triggered phosphatidylserine (PS) exposure, a signal for macrophage clearance of apoptotic cells. Our data suggest that Scythe cleavage may represent a marker for caspase-3 activation and implicate cytosolic re-localization of Scythe in the pathway of PS exposure.
大刀蛋白是一种核蛋白，已被牵连到黑腹果蝇细胞凋亡过程中；然而，其在哺乳动物细胞凋亡中的作用尚未完全阐明。在这里，我们发现 Caspase-3 可对大刀蛋白进行切割，此过程发生在细胞外（即 Fas/APO-1 介导的）和细胞内（即 staurosporine 诱导的）凋亡途径的激活之后。此外，这种 Caspase 依赖性切割与大刀蛋白从细胞核到细胞质的易位相关。我们还发现，大刀蛋白的细胞质再定位对于 Fas/APO-1 触发的磷脂酰丝氨酸（PS）暴露是必需的，PS 暴露是巨噬细胞清除凋亡细胞的信号。我们的数据表明，大刀蛋白的切割可能代表 Caspase-3 激活的一个标志物，并暗示了大刀蛋白在 PS 暴露途径中的细胞质再定位。
