Regulated targeting of cell death effectors to and from mitochondria.

人类细胞的蛋白质成分通过它们携带的靶向信号传递到它们适当的细胞内家园。现在看来，一小部分但很重要的关键调控蛋白是蛋白质劫持的受害者：这些蛋白质在特定的亚细胞隔间提供关键功能，但最初被阻止找到进入细胞内的家。只有在对特定的生理信号作出反应时，这些蛋白质才会释放出来，以找到它们的作用部位。人类细胞携带着一种分子上的死亡愿望。一组特定的基因编码的因子(蛋白质)将确保细胞自杀，或程序性细胞死亡，但这个程序只有在对准确的环境信号做出反应时才会启动。由于这些蛋白质的潜在致命性，它们中的几个会被蛋白质劫持，从而中和它们促进细胞死亡的能力。这些细胞死亡因子引起了人们的极大兴趣，了解它们在细胞内的位置和重新定位是至关重要的，因为它们代表了新的化疗药物的靶点。选择性地触发细胞自杀已被认为是防止处于许多癌症核心的不受控制的细胞增殖的一种敏感手段。我们正在研究一组关键的调节蛋白，以确定它们如何以及何时找到进入细胞内家园的途径，以及这种靶向如何影响它们在程序性细胞死亡中的功能。

The protein components of human cells travel to their appropriate intracellular homes by means of the targeting signals they carry. It now seems that a short, but important, list of key regulatory proteins are victims of protein hijacking: these proteins provide critical functions within a particular sub-cellular compartment, but are initially prevented from finding their way to this intracellular home. Only in response to specific physiological signals are these proteins released to find the site at which they act. Human cells carry a molecular death-wish. A specific set of genes encode factors (proteins) that would ensure cellular suicide, or programmed cell death, but this program is only turned on in response to precise environmental signals. Because of the potentially deadly nature of these proteins, several of them are subject to protein hijacking thereby neutralizing their ability to promote cell death. These cell death factors are of great interest, and understanding their location and relocation within cells is crucial, as they represent targets for novel chemotherapies. Selectively triggering a cellular suicide has been proposed as a sensitive means to preventing the uncontrolled cell proliferation at the heart of many cancers. We are studying a set of key regulatory proteins to determine how and when they find their way to the intracellular homes and how this targeting effects their function in programmed cell death.