Haining W N, Carboy-Newcomb C, Wei C L, Steller H
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Department of Biology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):4936-41. doi: 10.1073/pnas.96.9.4936.
Three genes-reaper, grim, and hid-are crucial to the regulation of programmed cell death in Drosophila melanogaster. Mutations involving all three genes virtually abolish apoptosis during development, and homozygous hid mutants die as embryos with extensive defects in apoptosis. Although Hid is central to apoptosis in Drosophila, it has no mammalian homologue identified to date. We present evidence that expression of Drosophila Hid in mammalian cells induces apoptosis. This activity is subject to regulation by inhibitors of mammalian cell death. We show that the N terminus of Hid, which is a region of homology with Reaper and Grim, is essential for Hid's function in mammalian cells. We demonstrate that Hid is localized to the mitochondria via a hydrophobic region at its C terminus and functionally interacts with BclXL. This study shows that the function of Hid as a death inducer in Drosophila is conserved in mammalian cells and argues for the existence of a mammalian homologue of this critical regulator of apoptosis.
三个基因——收割者基因（reaper）、严峻基因（grim）和隐藏基因（hid）——对于黑腹果蝇程序性细胞死亡的调控至关重要。涉及这三个基因的突变实际上会在发育过程中消除细胞凋亡，纯合的隐藏基因突变体作为胚胎死亡，在细胞凋亡方面存在广泛缺陷。尽管隐藏基因在果蝇的细胞凋亡中起核心作用，但迄今为止尚未鉴定出其哺乳动物同源物。我们提供的证据表明，果蝇隐藏基因在哺乳动物细胞中的表达会诱导细胞凋亡。这种活性受到哺乳动物细胞死亡抑制剂的调控。我们表明，隐藏基因的N末端，即与收割者基因和严峻基因具有同源性的区域，对于其在哺乳动物细胞中的功能至关重要。我们证明，隐藏基因通过其C末端的一个疏水区域定位于线粒体，并与BclXL在功能上相互作用。这项研究表明，隐藏基因在果蝇中作为死亡诱导剂的功能在哺乳动物细胞中是保守的，这为存在这种关键细胞凋亡调节因子的哺乳动物同源物提供了依据。
