کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1938572 | 1050742 | 2007 | 6 صفحه PDF | دانلود رایگان |
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 ∼40 times that was comparable with that of caspase-9 (∼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.
Journal: Biochemical and Biophysical Research Communications - Volume 356, Issue 4, 18 May 2007, Pages 1056–1061