Purification and cDNA cloning of a second apoptosis-related cysteine protease that cleaves and activates sterol regulatory element binding proteins.
Purification and cDNA cloning of a second apoptosis-related cysteine protease that cleaves and activates sterol regulatory element binding proteins.
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第二种与细胞凋亡相关的半胱氨酸蛋白酶的纯化和 cDNA 克隆，该蛋白酶可裂解并激活甾醇调节元件结合蛋白。
DOI：
10.1073/pnas.93.11.5437
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发表时间：
1996
影响因子：
11.1
通讯作者：
Goldstein,JL
中科院分区：
文献类型：
--
作者：
Pai,JT;Brown,MS;Goldstein,JL
我们从仓鼠肝脏中纯化出了第二种半胱氨酸蛋白酶，它可以裂解并激活甾醇调节元件结合蛋白（SREBP）。 cDNA 克隆表明，这种酶是 Mch3 的仓鼠等价物，Mch3 是一种与白细胞介素 1β 转换酶相关的人类酶。我们称这种酶为 Mch3/SCA-2。它与仓鼠 CPP32/SCA-1 具有 54% 的同一性，后者是一种半胱氨酸蛋白酶，之前已显示该酶可在基本螺旋-环-螺旋亮氨酸拉链结构域和膜附着结构域之间的保守 Asp 处切割 SREBP。这种切割释放出大约 460 个氨基酸的 NH2 末端片段，激活编码低密度脂蛋白受体和胆固醇合成酶的基因转录。 Mch3/SCA-2和CPP32/SCA-I被合成为无活性的30-35 kDa前体，其被认为在细胞凋亡期间被切割以产生大约20和大约10 kDa的活性片段。目前的数据进一步支持了这样的观点：SREBP 作为程序性细胞死亡程序的一部分被裂解和激活。
We have purified from hamster liver a second cysteine protease that cleaves and activates sterol regulatory element binding proteins (SREBPs). cDNA cloning revealed that this enzyme is the hamster equivalent of Mch3, a human enzyme that is related to the interleukin 1beta converting enzyme. We call this enzyme Mch3/SCA-2. It is 54% identical to hamster CPP32/SCA-1, a cysteine protease that was earlier shown to cleave SREBPs at a conserved Asp between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. This cleavage liberates an NH2-terminal fragment of approximately 460 amino acids that activates transcription of genes encoding the low density lipoprotein receptor and enzymes of cholesterol synthesis. Mch3/SCA-2 and CPP32/SCA-I are synthesized as inactive 30-35 kDa precursors that are thought to be cleaved during apoptosis to generate active fragments of approximately 20 and approximately 10 kDa. The current data lend further support to the notion that SREBPs are cleaved and activated as part of the program in programmed cell death.