A NOVEL HETERODIMERIC CYSTEINE PROTEASE IS REQUIRED FOR INTERLEUKIN-1-BETA PROCESSING IN MONOCYTES

A NOVEL HETERODIMERIC CYSTEINE PROTEASE IS REQUIRED FOR INTERLEUKIN-1-BETA PROCESSING IN MONOCYTES
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DOI:
10.1038/356768a0
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发表时间:
1992-04-30
期刊:
影响因子:
64.8
通讯作者:
TOCCI, MJ
TOCCI, MJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
THORNBERRY, NA;BULL, HG;TOCCI, MJ

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白细胞介素-1-β(IL-1-β)转化酶将IL-1-β前体裂解为成熟的IL-1-β,一种重要的炎症介质。作为一个独特的半胱氨酸蛋白酶的酶的鉴定和有效的肽醛抑制剂的设计进行了说明。互补DNA的纯化和克隆表明,IL-1-β-转化酶是由两个不同的亚基,来自一个单一的酶原,可能是通过自蛋白水解。选择性抑制人血单核细胞中的酶可阻断成熟IL-1-β的产生,表明其是潜在的治疗靶点。
Interleukin-1-beta (IL-1-beta)-converting enzyme cleaves the IL-1-beta precursor to mature IL-1-beta, an important mediator of inflammation. The identification of the enzyme as a unique cysteine protease and the design of potent peptide aldehyde inhibitors are described. Purification and cloning of the complementary DNA indicates that IL-1-beta-converting enzyme is composed of two nonidentical subunits that are derived from a single proenzyme, possibly by autoproteolysis. Selective inhibition of the enzyme in human blood monocytes blocks production of mature IL-1-beta, indicating that it is a potential therapeutic target.