Wu M X, Ao Z, Prasad K V, Wu R, Schlossman S F
Division of Tumor Immunology, Dana-Farber Cancer Institute, and the Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Science. 1998 Aug 14;281(5379):998-1001. doi: 10.1126/science.281.5379.998.
Transcription factors of the nuclear factor-kappaB/rel (NF-kappaB) family may be important in cell survival by regulating unidentified, anti-apoptotic genes. One such gene that protects cells from apoptosis induced by Fas or tumor necrosis factor type alpha (TNF), IEX-1L, is described here. Its transcription induced by TNF was decreased in cells with defective NF-kappaB activation, rendering them sensitive to TNF-induced apoptosis, which was abolished by transfection with IEX-1L. In support, overexpression of antisense IEX-1L partially blocked TNF-induced expression of IEX-1L and sensitized normal cells to killing. This study demonstrates a key role of IEX-1L in cellular resistance to TNF-induced apoptosis.
核因子-κB/rel（NF-κB）家族的转录因子可能通过调节未明确的抗凋亡基因在细胞存活中发挥重要作用。本文描述了一种这样的基因——IEX-1L，它可保护细胞免受Fas或α型肿瘤坏死因子（TNF）诱导的凋亡。在NF-κB激活缺陷的细胞中，TNF诱导的IEX-1L转录减少，使这些细胞对TNF诱导的凋亡敏感，而转染IEX-1L可消除这种敏感性。作为支持，反义IEX-1L的过表达部分阻断了TNF诱导的IEX-1L表达，并使正常细胞对杀伤敏感。这项研究证明了IEX-1L在细胞抵抗TNF诱导的凋亡中的关键作用。
