IDENTIFICATION OF A NOVEL SERINE THREONINE KINASE AND A NOVEL 15-KD PROTEIN AS POTENTIAL MEDIATORS OF THE GAMMA-INTERFERON-INDUCED CELL-DEATH
IDENTIFICATION OF A NOVEL SERINE THREONINE KINASE AND A NOVEL 15-KD PROTEIN AS POTENTIAL MEDIATORS OF THE GAMMA-INTERFERON-INDUCED CELL-DEATH
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DOI：
10.1101/gad.9.1.15
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发表时间：
1995-01-01
影响因子：
10.5
通讯作者：
KIMCHI, A
中科院分区：
文献类型：
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作者：
DEISS, LP;FEINSTEIN, E;KIMCHI, A
程序性细胞死亡通常是由某些细胞因子与其细胞表面受体的相互作用引发的。在这里，我们报告γ干扰素（IEN-γ）在HeLa细胞中诱导一种具有程序性细胞死亡的细胞学特征的细胞死亡。在这个系统中，我们鉴定了两个新基因，它们的表达对于执行这种类型的细胞死亡是必不可少的。拯救基于反义 cDNA 表达文库转染后细胞的阳性生长选择。反义RNA介导的两种新基因的失活可以保护细胞免受IFN-γ诱导的细胞死亡，但不能避免细胞因子的细胞抑制作用或坏死型细胞死亡。其中一个基因 (DAP-1) 表达为单个 2.4 kb mRNA，编码基本的、富含脯氨酸的 15 kD 蛋白质。第二个被转录为单个 6.3 kb mRNA，并编码独特的 160 kD 钙调蛋白依赖性丝氨酸/苏氨酸激酶（DAP 激酶），该激酶带有八个锚蛋白重复序列。两种 DAP 蛋白的表达水平被相应的反义 RNA 选择性降低。总而言之，这两个新基因被认为是 IFN-γ 诱导的程序性细胞死亡的正介体的候选基因。
Programmed cell death is often triggered by the interaction of some cytokines with their cell surface receptors. Here, we report that gamma interferon (IEN-gamma) induced in HeLa cells a type of cell death that had cytological characteristics of programmed cell death. In this system we have identified two novel genes whose expression was indispensable for the execution of this type of cell death. The rescue was based on positive growth selection of cells after transfection with antisense cDNA expression libraries. The antisense RNA-mediated inactivation of the two novel genes protected the cells from the IFN-gamma-induced cell death but not from the cytostatic effects of the cytokine or from a necrotic type of cell death. One of those genes (DAP-1) is expressed as a single 2.4-kb mRNA that codes for a basic, proline-rich, 15-kD protein. The second is transcribed into a single 6.3-kb mRNA and codes for a unique 160-kD calmodulin-dependent serine/threonine kinase (DAP kinase) that carries eight ankyrin repeats. The expression levels of the two DAP proteins were selectively reduced by the corresponding antisense RNAs. Altogether, it is suggested that these two novel genes are candidates for positive mediators of programmed cell death that is induced by IFN-gamma.