bcl-XL is the major bcl-x mRNA form expressed during murine development and its product localizes to mitochondria.
bcl-XL is the major bcl-x mRNA form expressed during murine development and its product localizes to mitochondria.
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发表时间：
1994-10
期刊：
影响因子：
4.6
通讯作者：
M. González‐García;Rafael Pérez-Ballestero;Liyun Ding;L. Duan;L. Boise;C. Thompson;G. Núñez
中科院分区：
文献类型：
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作者：
M. González‐García;Rafael Pérez-Ballestero;Liyun Ding;L. Duan;L. Boise;C. Thompson;G. Núñez
动物细胞死亡的大多数例子是由一种在垂死细胞内被激活的遗传程序控制的。凋亡过程进一步受到一组作为细胞死亡抑制因子的基因的调控。其中，bcl-2在多种胚胎和出生后组织中表达，这表明bcl-2在器官发生和组织稳态中起着关键作用。令人惊讶的是，靶向破坏bcl-2的突变小鼠在出生时表现正常，淋巴组织完全成熟，然后在2-5周龄时屈服于暴发性淋巴细胞减少症和多囊肾病。这表明可能有除bcl-2以外的基因在发育过程中调控细胞凋亡。为了开始研究这种可能性，我们克隆了小鼠bcl-x基因并对其进行了表征，其人类对应基因与bcl-2具有惊人的同源性。预测的小鼠bcl-xL基因产物与人类的氨基酸同源性很高（97%）。与Bcl-2一样，小鼠bcl-xL基因产物可作为生长因子停用后细胞死亡的显性抑制剂。此外，通过bcl-xL标签表达系统评估，大部分bcl-xL产物定位于线粒体外围，这表明Bcl-2和bcl-xL蛋白通过类似的机制预防细胞死亡。bcl-xL是胚胎和成体组织中表达量最多的bcl-x mRNA种类。在胚胎发育过程中，bcl-xL mRNA的表达水平高于bcl-2，在骨髓、脑、肾和胸腺等成体器官中，bcl-xL mRNA的表达水平高于bcl-2。除了bcl-xL外，我们还鉴定了另一种形式的bcl-x mRNA，即bcl-x β，它来自未剪接的bcl-x转录物。bcl-x β mRNA在各种胚胎和出生后组织中表达。令人惊讶的是，bcl-xS（程序性细胞死亡的负调节因子）的表达通过灵敏的s1核酸酶测定和小鼠组织的聚合酶链反应分析无法检测到。基于其组织和发育表达模式，bcl-x可能在发育和组织稳态过程中调控细胞死亡中发挥重要作用。
Most examples of cell death in animals are controlled by a genetic program that is activated within the dying cell. The apoptotic process is further regulated by a set of genes that act as repressors of cell death. Of these, bcl-2 is expressed in a variety of embryonic and postnatal tissues which suggests a critical role for bcl-2 in organogenesis and tissue homeostasis. Surprisingly, mutant mice with targeted disruption of bcl-2 appear normal at birth and complete maturation of lymphoid tissues before succumbing to fulminant lymphopenia and polycystic renal disease by 2-5 weeks of age. This suggests that there may be genes other than bcl-2 that can regulate apoptosis during development. To begin to investigate this possibility, we have cloned and characterized the murine bcl-x gene, whose human counterpart displays striking homology to bcl-2. The predicted murine bcl-xL gene product exhibits a high level of amino acid identity (97%) to its human counterpart. Just like Bcl-2, the murine bcl-xL gene product can act as a dominant inhibitor of cell death upon growth factor withdrawal. In addition, the bulk of the bcl-xL product localizes to the periphery of mitochondria as assessed by a bcl-xL-tag expression system, suggesting that both Bcl-2 and Bcl-xL proteins prevent cell death by a similar mechanism. bcl-xL is the most abundant bcl-x mRNA species expressed in embryonic and adult tissues. The levels of bcl-xL mRNA appear higher than those of bcl-2 during embryonal development and in several adult organs including bone marrow, brain, kidney and thymus. In addition to bcl-xL, we have identified another form of bcl-x mRNA, bcl-x beta, that results from an unspliced bcl-x transcript. bcl-x beta mRNA is expressed in various embryonic and postnatal tissues. Surprisingly, the expression of bcl-xS (a negative regulator of programmed cell death) was undetectable by a sensitive S1-nuclease assay and polymerase chain reaction analysis of mouse tissues. Based on its tissue and developmental patterns of expression, it appears that bcl-x may play an important role in the regulation of cell death during development and tissue homeostasis.