Both dimerization and interdomain processing are essential for caspase-4 activation
Both dimerization and interdomain processing are essential for caspase-4 activation
复制标题
DOI：
10.1016/j.bbrc.2007.03.102
复制
发表时间：
2007-05-18
影响因子：
3.1
通讯作者：
Park, Il-Seon
中科院分区：
文献类型：
--
作者：
Karki, Pratap;Dahal, Giri Raj;Park, Il-Seon
炎症性半胱天冬酶家族的一个亚组（-1、-4、-5、-11和-12）在细胞因子成熟和炎症过程中起重要作用，但它们的调控不如启动子和效应子半胱天冬酶那样清楚。在这里，caspase-4激活的生化机制阐明。使用柠檬酸盐，一种众所周知的增强单体-二聚体转变的稳液剂，半胱天冬酶-4被激活了类似于40倍，这与半胱天冬酶-9相当（类似于75倍增量）。对于单体半胱天冬酶-4，活化反应主要是双分子的（n = 1.67 +/- 0.04）。此外，结构域间切割也负责激活caspase-4超过100倍，再次与效应caspase的蛋白水解加工被认为是唯一的激活机制。因此，胱天蛋白酶-4显示了二聚化和蛋白水解之间的协同作用的一种新的激活机制，其与已建立的引发剂二聚化和效应器胱天蛋白酶的结构域间裂解的激活机制截然不同。(c)Elsevier Inc. All right reserved.
A subgroup of caspase family of inflammatory caspases (-1, -4, -5, -11, and -12) play important role during cytokine maturation and inflammation but their regulation is not well understood as much as the initiator and effector caspases. Here, the biochemical mechanism of caspase-4 activation is elucidated. With citrate, a well-known kosmotrope to enhance the monomer-dimer transition, caspase-4 was activated similar to 40 times that was comparable with that of caspase-9 (similar to 75-fold increments). The activation reaction was mainly bimolecular (n = 1.67 +/- 0.04) for monomeric caspase-4. In addition, the interdomain cleavage was also responsible to activate caspase-4 more than 100-fold, again comparable with that of effector caspases where the proteolytic processing is considered as the sole activation mechanism. Thus, caspase-4 shows a novel activation mechanism of the synergism between dimerization and proteolysis that sharply differs from the established activation mechanism of dimerization for initiators and interdomain cleavage for effector caspases. (c) Elsevier Inc. All right reserved.