Caspase-mediated proteolysis during apoptosis: insights from apoptotic neutrophils
Caspase-mediated proteolysis during apoptosis: insights from apoptotic neutrophils
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DOI：
10.1016/s0014-5793(98)00004-0
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发表时间：
1998-01-30
期刊：
影响因子：
3.5
通讯作者：
Rosen, A
中科院分区：
文献类型：
--
作者：
Sanghavi, DM;Thelen, M;Rosen, A
凋亡是由半胱天冬酶（白细胞介素- 1 β转换酶同源物）的激活启动的，它引起几种在结构或稳态途径中起作用的死亡底物的协调切割。底物切割与细胞凋亡之间的关系尚不清楚，也不清楚特定底物的切割是否是细胞凋亡的关键条件。人类中性粒细胞为细胞凋亡过程中特定底物的蛋白水解作用提供了新的见解，因为成熟的中性粒细胞中只存在半胱天冬酶底物的一个子集。在我们筛选的死亡底物中，PARP、核有丝分裂器蛋白（NuMA）、U1小核糖核蛋白（U1- 70kda）的70kDa亚基和dna依赖性蛋白激酶（DNA-PKcs）的催化亚基在非凋亡中性粒细胞中未检测到；相比之下，层粘连蛋白B和fodrin的含量与其他细胞相似。Caspase-3活性在新分离的中性粒细胞中不存在，但在体外中性粒细胞老化时检测到，与形态学和生化凋亡的开始一致。PARP、NuMA、U1-70kDa和DNA-PKcs在非凋亡中性粒细胞中的缺失表明，这些不是关键的抗凋亡蛋白，它们的片段不是中性粒细胞凋亡途径所需的组分。这些研究强调了caspase激活在细胞凋亡机制中的保守作用，并关注了一些保守的结构底物作为细胞凋亡中蛋白水解信号的潜在转导。(C) 1998年欧洲生化学会联合会。
Apoptosis is initiated by activation of caspases (interleukin 1 beta-converting enzyme homologues), which cause coordinated cleavage of several death substrates that function in structural or homeostatic pathways. The relationship between substrate cleavage and apoptosis is not yet known, nor is it clear whether cleavage of specific substrates is a critical requirement for apoptosis. The human neutrophil provides novel insights into the roles of proteolysis of specific substrates during apoptosis, since only a subset of caspase substrates are present in mature neutrophils. Of the death substrates we screened, PARP, the nuclear mitotic apparatus protein (NuMA), the 70 kDa subunit of the U1 small ribonucleoprotein (U1-70kDa) and the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) mere not detected in non-apoptotic neutrophils; in contrast, lamin B and fodrin mere present in amounts similar to those found in other cells. Caspase-3 activity was absent in freshly isolated neutrophils, but was detected when neutrophils were aged in vitro, coincident with the onset of morphologic and biochemical apoptosis. The absence of PARP, NuMA, U1-70kDa and DNA-PKcs in non-apoptotic neutrophils suggests that these are not critical anti-apoptotic proteins, and that their fragments are not required components of the neutrophil apoptotic pathway. These studies highlight the conserved role of caspase activation in the apoptotic mechanism, and focus attention on several conserved structural substrates as potential transducers of the proteolytic signal in apoptosis. (C) 1998 Federation of European Biochemical Societies.