Peter M E, Heufelder A E, Hengartner M O
Tumor Immunology Program, German Cancer Research Center, Heidelberg.
Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12736-7. doi: 10.1073/pnas.94.24.12736.
Apoptosis, also called programmed cell death, has attracted great attention in recent years. After its discovery by Carl Vogt in 1842, apoptosis research was dormant for more than a century. Its rediscovery in the second half of this century, and the coining of the term apoptosis in 1972 by Kerr, Wyllie, and Currie, ignited an unparalleled interest in this field of science. The number of publications related to apoptosis has been growing exponentially every year ever since. This is mainly due to three major advances, two of which have been made recently and one that is currently seen. First, studies with the small nematode Caenorhabditis elegans have identified a number of apoptosis regulating genes--the first evidence that cell death is an active process under genetic control. Many of these genes have mammalian homologs that, like their worm counterparts, seem to regulate mammalian apoptosis. Second, elucidation of the signal transduction pathways of apoptosis has lead especially to the identification of specific death signaling molecules such as a new family of cysteine proteases, the caspases. Third, it has now become clear that many diseases are characterized by dysregulation of apoptotic programs. Many of these programs involve a family of receptors and their ligands, the death receptor/ligand family. The hope now is to interfere with apoptosis regulation in these systems and to develop new therapeutic concepts.
细胞凋亡,也称为程序性细胞死亡,近年来备受关注。1842年卡尔·沃格特发现细胞凋亡后,其研究沉寂了一个多世纪。本世纪下半叶它被重新发现,1972年克尔、威利和柯里创造了“细胞凋亡”这个术语,引发了对这一科学领域前所未有的兴趣。从那以后,每年与细胞凋亡相关的出版物数量呈指数级增长。这主要归功于三项重大进展,其中两项是最近取得的,一项是目前正在出现的。首先,对线虫秀丽隐杆线虫的研究鉴定出了许多细胞凋亡调节基因——这是细胞死亡是一个受基因控制的主动过程的首个证据。这些基因中的许多在哺乳动物中有同源物,与线虫中的对应物一样,似乎也调节哺乳动物的细胞凋亡。其次,对细胞凋亡信号转导途径的阐明尤其导致了特定死亡信号分子的鉴定,比如一个新的半胱氨酸蛋白酶家族——胱天蛋白酶。第三,现在已经清楚,许多疾病的特征是细胞凋亡程序失调。这些程序中的许多涉及一个受体家族及其配体,即死亡受体/配体家族。现在的希望是在这些系统中干扰细胞凋亡调节并开发新的治疗理念。