Specific cleavage of the 70-kDa protein component of the U1 small nuclear ribonucleoprotein is a characteristic biochemical feature of apoptotic cell death.

Specific cleavage of the 70-kDa protein component of the U1 small nuclear ribonucleoprotein is a characteristic biochemical feature of apoptotic cell death.
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DOI:
10.1016/s0021-9258(18)47343-7
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发表时间:
1994-12
期刊:
The Journal of biological chemistry
影响因子:
--
通讯作者:
L. Casciola-Rosen;Douglas K. Miller;G. Anhalt;A. Rosen
L. Casciola-Rosen;Douglas K. Miller;G. Anhalt;A. Rosen
中科院分区:
其他
文献类型:
--
作者:
L. Casciola-Rosen;Douglas K. Miller;G. Anhalt;A. Rosen

文献摘要

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U1小核核糖核蛋白颗粒对于前体mRNA的剪接是必不可少的,这种活性取决于U1颗粒的RNA和蛋白质组分。在这种剪接反应中功能重要的U1特异性蛋白质之一是70-kDa蛋白质(U1- 70 kDa)。我们在这里报告,U1- 70 kDa的特异性裂解在凋亡细胞,导致在40 kDa的片段的产生。这种分裂的动力学与人口中的细胞凋亡形态的外观相吻合,观察到的40 kDa片段的比例显着增加,已成为脱离基层的凋亡细胞。虽然切割U1- 70 kDa的活性的抑制剂特性表明白细胞介素1 β转换酶(ICE)可能是负责的,但特异性ICE抑制剂N-(N-乙酰基-酪氨酸-缬氨酰-丙氨酰)-3-氨基-4-氧代丁酸(YVAD-CHO)不能阻止切割,并且U1- 70 kDa在体外不被纯化的ICE切割。进一步研究这种新的切割和负责的酶将产生有关蛋白水解事件的信息,这些事件可能是细胞凋亡机制和控制的核心。
The U1 small nuclear ribonucleoprotein particle is essential for splicing of precursor mRNA, an activity that depends upon both the RNA and protein components of the U1 particle. One of the U1-specific proteins that is functionally important in this splicing reaction is the 70-kDa protein (U1-70kDa). We report here that U1-70kDa is specifically cleaved in apoptotic cells, resulting in the generation of a 40-kDa fragment. The kinetics of this cleavage coincided with the appearance of cells with apoptotic morphology in the population, and the proportion of 40-kDa fragment observed was markedly increased in apoptotic cells that had become detached from the substratum. Although the inhibitor characteristics of the activity cleaving U1-70kDa suggest that interleukin 1 beta-converting enzyme (ICE) might be responsible, the specific ICE inhibitor N-(N-acetyl-tyrosinyl-valinyl-alaninyl)-3-amino-4-oxob utanoic acid (YVAD-CHO) did not prevent cleavage, and U1-70kDa was not cleaved by purified ICE in vitro. Further study of this novel cleavage and the enzyme responsible will yield information about proteolytic events that might be central in the mechanism and control of apoptosis.