Fas-induced DNA fragmentation and proteolysis of nuclear proteins
Fas-induced DNA fragmentation and proteolysis of nuclear proteins
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DOI：
10.1046/j.1365-2443.1998.00189.x
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发表时间：
1998-05-01
期刊：
影响因子：
2.1
通讯作者：
Nagata, S
中科院分区：
文献类型：
--
作者：
Kawahara, A;Enari, M;Nagata, S
背景：Fas是肿瘤坏死因子受体家族的成员。结果：制备了caspase3和caspase6的特异性荧光底物(MCA-DEV-DAPK[DNP]和MCA-VEVDAPK[DNP])，发现在Fas参与人Jurkat的过程中，caspase3和caspase6样酶的数量逐渐增加，这种caspase的激活与聚(ADP-核糖)聚合酶和层蛋白B1的切割以及DNA片段化密切相关。当将重组caspase加入JURKAT细胞提取液中时，caspase 3产生类似caspase 6的活性酶，而caspase 6则激活caspase 3酶，表明这两种酶可以相互激活，caspase处理的细胞提取液和Fas激活的细胞提取液都能引起核蛋白的蛋白分解和DNA的降解。结论：在caspase级联反应的某一阶段，caspase相互激活，放大了细胞的凋亡信号，Caspase下游的caspase引起核蛋白的降解和DNA的降解。
Background: Fas is a member of the tumour necrosis factor (TNF) receptor family. Activation of Fas by its ligand or an agonistic anti-Fas antibody causes apoptosis in Fas-bearing cells, by activating various members of the caspase family,Results: Specific fluorogenic substrates (MCA-DEV-DAPK[dnp] and MCA-VEVDAPK[dnp]) for caspases 3 and 6 were prepared, Using these substrates, a gradual increase of the caspase 3- and 6-like proteases were detected during the Fas engagement in human Jurkat, This activation of caspases correlated well with the cleavage of poly(ADP-ribose) polymerase and lamin B1, as well as with DNA fragmentation. When the recombinant caspases were added to the extracts from jurkat cells, caspase 3 produced active caspase 6-like protease, while caspase 6 activated the caspase 3 protease, suggesting that these proteases can activate each other, The caspase-treated cell extracts, as well as the extracts from the Fas-activated cells, caused the proteolysis of nuclear proteins and DNA degradation. The cleavage of nuclear proteins was inhibited by caspase inhibitors, while the same inhibitors had no effect on DNA degradation, nuclear cleavageConclusions: At one stage of the caspase cascade, caspases activate each other, and amplify the apoptotic signal, Caspases downstream of the cascade then cause the proteolysis of nuclear proteins and DNA degradation.