Purification of an Interleukin-1 Converting Enzyme-related Cysteine Protease That Cleaves Sterol Regulatory Element-binding Proteins between the Leucine Zipper and Transmembrane Domains (*)
Purification of an Interleukin-1 Converting Enzyme-related Cysteine Protease That Cleaves Sterol Regulatory Element-binding Proteins between the Leucine Zipper and Transmembrane Domains (*)
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纯化白细胞介素 1 转换酶相关的半胱氨酸蛋白酶，该蛋白酶可切割亮氨酸拉链和跨膜结构域之间的甾醇调节元件结合蛋白 (*)
DOI：
--
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发表时间：
1995
影响因子：
4.8
通讯作者：
M. Brown
中科院分区：
文献类型：
--
作者：
X. Wang;J. Pai;E. A. Wiedenfeld;J. Medina;C. Slaughter;J. Goldstein;M. Brown
我们描述了一种蛋白酶，在体外切割甾醇调节元件结合蛋白-1（SREBP-1）和SREBP-2的表征和纯化。切割发生在碱性螺旋-环-螺旋-亮氨酸拉链和每个SREBP的第一个跨膜结构域之间。这是SREBP被固醇调节的蛋白酶生理性切割的区域，该蛋白酶释放激活低密度脂蛋白受体和3-羟基-3-甲基戊二酰辅酶A合酶基因转录的NH 2末端片段。该切割酶，命名为SREBP切割活性（SCA），属于白细胞介素-1 β-转化酶（ICE）家族的一类新的半胱氨酸蛋白酶，所有这些酶都在天冬氨酸残基处切割。与ICE一样，SCA在胞质溶胶中无活性，在体外30°C孵育可激活SCA。SCA对丝氨酸、乙酰丝氨酸和金属蛋白酶的抑制剂有抗性，但对N-乙基马来酰亚胺敏感。该酶切割保守序列（S/DEPDSP）的Asp和Ser之间的SREBP-1和SREBP-2。该活性被四肽醛Ac-Asp-Glu-Ala-Asp-aldehyde（Ac-DEAD-CHO）阻断。从仓鼠肝脏SCA的纯化制剂中含有一个突出的20 kDa的多肽，可以用[14 C]碘乙酸标记。用Ac-DEAD-CHO封闭标记。该多肽的部分氨基酸序列显示，它是仓鼠相当于人CPP 32，一种推定的蛋白酶，其cDNA最近被确定凭借与ICE的序列同源性。CPP 32和ICE与动物细胞的凋亡有关。SCA/CPP 32是否在体内参与固醇调节的SREBP激活，或者它是否在凋亡过程中激活SREBP，仍有待确定。
We describe the characterization and purification of a protease that cleaves sterol regulatory element-binding protein-1 (SREBP-1) and SREBP-2 in vitro. Cleavage occurs between the basic helix-loop-helix-leucine zipper and the first transmembrane domain of each SREBP. This is the region in which the SREBPs are cleaved physiologically by a sterol-regulated protease that releases an NH2-terminal fragment that activates transcription of the genes for the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl CoA synthase. The cleavage enzyme, designated SREBP cleavage activity (SCA), belongs to a new class of cysteine proteases of the interleukin-1β-converting enzyme (ICE) family, all of which cleave at aspartic acid residues. Like ICE, SCA was inactive in cytosol, and it was activated in vitro by incubation at 30°C. SCA was resistant to inhibitors of serine, aspartyl, and metalloproteases, but it was sensitive to N-ethylmaleimide. The enzyme cleaved SREBP-1 and SREBP-2 between the Asp and Ser of a conserved sequence (S/DEPDSP). The activity was blocked by a tetrapeptide aldehyde, Ac-Asp-Glu-Ala-Asp-aldehyde (Ac-DEAD-CHO). A purified preparation of SCA from hamster liver contained a prominent 20-kDa polypeptide that could be labeled with [14C]iodoacetic acid. Labeling was blocked by Ac-DEAD-CHO. Partial amino acid sequence of this polypeptide revealed that it was the hamster equivalent of human CPP32, a putative protease whose cDNA was recently identified by virtue of sequence homology to ICE. CPP32 and ICE have been implicated in apoptosis in animal cells. Whether SCA/CPP32 participates in vivo in the sterol-regulated activation of SREBP, or whether it activates SREBPs during apoptosis, remains to be determined.
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DOI：
10.1016/s0021-9258(18)47344-9
发表时间：
1994-12
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
T. Fernandes‐Alnemri;G. Litwack;E. Alnemri
通讯作者：
T. Fernandes‐Alnemri;G. Litwack;E. Alnemri
DOI：
10.1073/pnas.90.24.11603
发表时间：
1993-12-15
影响因子：
11.1
作者：
HUA, XX;YOKOYAMA, C;WANG, XD
通讯作者：
WANG, XD
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Kunz,D;Gerard,NP;Gerard,C
通讯作者：
Gerard,C
DOI：
--
发表时间：
1993-07
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
M. Briggs;C. Yokoyama;Xiaodong Wang;Michael S. Brown;J. Goldstein
通讯作者：
M. Briggs;C. Yokoyama;Xiaodong Wang;Michael S. Brown;J. Goldstein
影响因子：
4.4
作者：
HUA, XX;WU, J;HOBBS, HH
通讯作者：
HOBBS, HH