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FLIP(L): the pseudo‐caspase
The FEBS Journal ( IF 5.5 ) Pub Date : 2020-02-24 , DOI: 10.1111/febs.15260
Peter Smyth 1 , Tamas Sessler 1 , Christopher J. Scott 1 , Daniel B. Longley 1
Affiliation  

Possessing structural homology with their active enzyme counterparts but lacking catalytic activity, pseudoenzymes have been identified for all major enzyme groups. Caspases are a family of cysteine‐dependent aspartate‐directed proteases that play essential roles in regulating cell death and inflammation. Here, we discuss the only human pseudo‐caspase, FLIP(L), a paralog of the apoptosis‐initiating caspases, caspase‐8 and caspase‐10. FLIP(L) has been shown to play a key role in regulating the processing and activity of caspase‐8, thereby modulating apoptotic signaling mediated by death receptors (such as TRAIL‐R1/R2), TNF receptor‐1 (TNFR1), and Toll‐like receptors. In this review, these canonical roles of FLIP(L) are discussed. Additionally, a range of nonclassical pseudoenzyme roles are described, in which FLIP(L) functions independently of caspase‐8. These nonclassical pseudoenzyme functions enable FLIP(L) to play key roles in the regulation of a wide range of biological processes beyond its canonical roles as a modulator of cell death.

中文翻译:

FLIP(L):准胱天蛋白酶

具有与它们的活性酶对应物的结构同源性,但缺乏催化活性,已鉴定出所有主要酶基团的假酶。胱天蛋白酶是半胱氨酸依赖性天冬氨酸定向蛋白酶的家族,在调节细胞死亡和炎症中起重要作用。在这里,我们讨论了唯一的人类假性半胱天冬酶FLIP(L),它是启动凋亡的半胱天冬酶caspase-8和caspase-10的旁系同源物。已证明FLIP(L)在调节caspase-8的加工和活性中起关键作用,从而调节由死亡受体(如TRAIL-R1 / R2),TNF受体-1(TNFR1)和收费型受体。在这篇综述中,讨论了FLIP(L)的这些规范作用。此外,还介绍了一系列非经典假酶作用,其中FLIP(L)的功能独立于caspase-8。这些非经典的伪酶功能使FLIP(L)在调节广泛的生物过程中发挥关键作用,而不仅仅是作为细胞死亡的调节剂。
更新日期:2020-02-24
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