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Regulation of human cathepsin B by alternative mRNA splicing: homeostasis, fatal errors and cell death

机译:通过选择性的mRNA剪接调节人组织蛋白酶B:体内稳态,致命错误和细胞死亡

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摘要

One of the control mechanisms of cathepsin B biosynthesis and trafficking operates through alternative splicing of pre-mRNA. An mRNA lacking exon 2 is more efficiently translated than that containing all exons, and may be responsible for elevated biosynthesis and enzyme routing to the extracellular space, with critical consequences for connective tissue integrity in pathologies such as cancer and arthritis. mRNA missing exons 2 and 3 encodes a truncated procathepsin B form that is targeted to mitochondria. This enzyme variant is catalytically inactive because it cannot properly fold. However, it provokes a cascade of events, which result first in morphological changes in intracellular organelles and the nucleus, finally leading to cell death
机译:组织蛋白酶B生物合成和运输的控制机制之一是通过pre-mRNA的可变剪接来实现的。缺少外显子2的mRNA比包含所有外显子的mRNA更有效地翻译,并且可能导致生物合成增加和酶向细胞外空间的转移,对诸如癌症和关节炎等病理性结缔组织完整性具有至关重要的影响。缺失外显子2和3的mRNA编码靶向线粒体的截短的组织蛋白酶B形式。该酶变体没有催化折叠性,因为它无法正确折叠。然而,它引起了一系列事件,首先导致细胞内细胞器和细胞核的形态变化,最后导致细胞死亡。

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