Review Cell Death: Critical Control Points Another Line of Evidence for the Importance of Caspases in Cell Death Came From
Review Cell Death: Critical Control Points Another Line of Evidence for the Importance of Caspases in Cell Death Came From
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N. Danial;S. Korsmeyer;H Robert
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作者：
N. Danial;S. Korsmeyer;H Robert
霍维茨有能力使C. elegans，在Dana-Farber癌症研究所为了鉴定调节哈佛医学院所有131个体细胞死亡的基因（Ellis和Horvitz，1986）。由于他们在发育遗传学和程序性细胞死亡方面的开创性贡献，布伦纳、霍维茨和苏尔斯顿三人获得了2002年诺贝尔奖。最初，两个基因，程序性细胞死亡是一个独特的遗传和bio-ced-3和ced-4被指出是绝对必要的化学途径必不可少的后生动物。一个完整的所有死亡。然而，另一个基因ced-9是成功胚胎所需的死亡途径，以防止细胞死亡，并首次通过获得发育和维持正常组织功能突变n1950来确定，该突变主要阻断稳态。细胞凋亡已被证明是所有体细胞死亡之间的紧密联系（Hengartner和Horvitz，1994 a）。与其他重要的细胞通路交织在一起。已证实的是，在细胞死亡BCL-2癌基因中的关键控制点的哺乳动物化的蠕虫同源物，其已被证明阻止途径已经产生了基本的凋亡细胞死亡的基本见解。此外，哺乳动物BCL-2是生物学的，也为新的能够在C.秀丽隐杆线虫（Vaux等，1992;治疗学。Hengartner和Horvitz，1994 b），表明这种细胞死亡途径的进化保守性。程序性细胞死亡（Lockshin和威廉姆斯，1965）ced-3的克隆和表征提供了细胞凋亡及其形态学表现（Kerr等人，1972）是一种保守的途径，其基本原理是执行细胞死亡。ced-3编码一种与在所有后生动物中起作用的相关蛋白。哺乳动物白细胞介素1 β转化酶（ICE）胚胎发育期间的细胞死亡对于成功或参与炎症是必不可少的（Yuan等人，1993年）。ced-3或ICE在哺乳动物细胞中诱导细胞组织的表达和复杂多细胞的加工。分化细胞死亡的进化出现。ICE成为一类需要控制死亡和分裂的蛋白酶家族的第一个成员（caspase-1），以保持相邻细胞相互依赖地切割具有天冬氨酸（aspase）的基序，从而破坏和确保每个细胞谱系的适当平衡。名称半胱天冬酶（Thornberry和Lazebnik，1998）。细胞凋亡也在成年生物体中起作用，以维持半胱天冬酶作为非活性酶原产生，以维持正常的细胞内稳态。这一点尤其重要。
Horvitz had the insight to mutagenize C. elegans, in Dana-Farber Cancer Institute order to identify genes regulating all 131 somatic cell Harvard Medical School deaths (Ellis and Horvitz, 1986). For their pioneering con-Boston, Massachusetts 02115 tributions to developmental genetics and programmed cell death, the triumvirate of Brenner, Horvitz, and Sul-ston received the 2002 Nobel Prize. Initially, two genes, Programmed cell death is a distinct genetic and bio-ced-3 and ced-4 were noted to be absolutely required chemical pathway essential to metazoans. An intact for all deaths. Whereas, another gene, ced-9 is required death pathway is required for successful embryonic to prevent cell death and was first identified by a gain-development and the maintenance of normal tissue of-function mutation n1950, which dominantly blocked homeostasis. Apoptosis has proven to be tightly inter-all somatic cell death (Hengartner and Horvitz, 1994a). woven with other essential cell pathways. The iden-ced-9 proved to be the worm homolog of the mammalian tification of critical control points in the cell death BCL-2 oncogene, which had been shown to prevent pathway has yielded fundamental insights for basic apoptotic cell death. Moreover, mammalian BCL-2 was biology, as well as provided rational targets for new capable of functioning in C. elegans (Vaux et al., 1992; therapeutics. Hengartner and Horvitz, 1994b) suggesting the evolutionary conservation of this cell death pathway. Programmed cell death (Lockshin and Williams, 1965) The cloning and characterization of ced-3 provided a and its morphologic manifestation of apoptosis (Kerr et critical insight into how the core apoptotic machinery al., 1972) is a conserved pathway that in its basic tenets executes cell death. ced-3 encoded a protein related to appears operative in all metazoans. Cell deaths during the mammalian interleukin 1 converting enzyme (ICE) embryonic development are essential for successful or-involved in inflammation (Yuan et al., 1993). Expression ganogenesis and the crafting of complex multicellular of either ced-3 or ICE in mammalian cells induced cell tissues. The evolutionary advent of differentiated cell death. ICE became the first member (caspase-1) of a types may have necessitated controlling death as well family of proteases dependent on a cysteine nucleophile as division in order to keep neighboring cells interdepen-to cleave motifs possessing aspartic acid (aspase), thus dent and insure the proper balance of each cell lineage. the name caspase (Thornberry and Lazebnik, 1998). Apoptosis also operates in adult organisms to maintain Caspases are produced as inactive zymogens pos-normal cellular homeostasis. This is especially critical …