Related membrane domains in proteins of sterol sensing and cell signaling provide a glimpse of treasures still buried within the dynamic realm of intracellular metabolic regulation.
Related membrane domains in proteins of sterol sensing and cell signaling provide a glimpse of treasures still buried within the dynamic realm of intracellular metabolic regulation.
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甾醇传感和细胞信号传导蛋白中的相关膜结构域让我们得以一睹仍埋藏在细胞内代谢调节动态领域中的宝藏。
DOI：
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发表时间：
1998
影响因子：
4.4
通讯作者：
J. Rosenfeld
中科院分区：
文献类型：
--
作者：
T. Osborne;J. Rosenfeld
最近在胆固醇代谢调节方面的发现已经证明了一个两步蛋白水解途径，该途径调节了甾醇调节元件结合蛋白的核靶向。甾醇调节元件结合蛋白裂解激活蛋白是一种新发现的调节甾醇调节元件结合蛋白水解成熟的蛋白。它包含一个结构域，在序列上与胆固醇生物合成的速率控制酶，3-羟基-3-甲基戊二酰辅酶a还原酶的跨膜区域非常相似。还原酶的膜结构域参与胆固醇对其翻译后的调节。细胞内胆固醇储存病的分子缺陷，Niemann-Pick型C，最近也被发现。令人惊讶的是，受影响的基因编码的蛋白质与3-羟基-3-甲基戊二酰还原酶和固醇调节元件结合蛋白裂解激活蛋白中保守的膜结构域相似。此外，甾醇修饰的刺猬形态原的细胞表面受体patch也包含一个与假定的甾醇监测结构域显著相似的膜结构域。这些最新进展表明，细胞内固醇水平和细胞信号传导的感知机制是基于关键调节蛋白中相关膜结构域的功能。
Recent discoveries in the regulation of cholesterol metabolism have documented a two step proteolytic pathway that regulates nuclear targeting of the sterol regulatory element binding proteins. Sterol regulatory element binding protein cleavage activating protein is a newly identified protein that modulates the proteolytic maturation of the sterol regulatory element binding proteins. It contains a domain that is quite similar in sequence to the membrane spanning region of the rate controlling enzyme of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase. The membrane domain of the reductase is involved in its post-translational regulation by cholesterol. The molecular defect in the intracellular cholesterol storage disease, Niemann-Pick type C, has also recently been identified. Surprisingly, the affected gene encodes a protein with similarity to the membrane domains that are conserved in 3-hydroxy-3-methylglutaryl reductase and sterol regulatory element binding protein cleavage activating protein. Furthermore, the cell surface receptor for the sterol modified hedgehog morphogen, Patched, also contains a membrane domain with significant similarity to this putative sterol monitoring domain. These recent developments suggest a common mechanism for sensing intracellular sterol levels and cell signaling, which is based on the function of related membrane domains that are contained in key regulatory proteins.
影响因子：
56.9
作者：
BROWN, MS;GOLDSTEIN, JL
通讯作者：
GOLDSTEIN, JL
SREBP 裂解激活蛋白的单个密码子中反复发生的 G 到 A 替换会导致三种突变的中国仓鼠卵巢细胞系产生甾醇抗性。
DOI：
10.1073/pnas.93.24.13709
发表时间：
1996
影响因子：
11.1
作者：
Nohturfft,A;Hua,X;Brown,MS;Goldstein,JL
通讯作者：
Goldstein,JL