Cholesterol modification of hedgehog signaling proteins in animal development
Cholesterol modification of hedgehog signaling proteins in animal development
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DOI：
10.1126/science.274.5285.255
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发表时间：
1996-10-11
期刊：
影响因子：
56.9
通讯作者：
Beachy, PA
中科院分区：
文献类型：
--
作者：
Porter, JA;Young, KE;Beachy, PA
Hedgehog (Hh) 蛋白包含一系列分泌信号分子，对于动物胚胎发生中多种结构的形成至关重要。在生物合成过程中，Hh 经历由其羧基末端结构域介导的自裂解反应，产生脂质修饰的氨基末端片段，负责所有已知的 Hh 信号传导活性。据报道，胆固醇是在自动加工过程中共价连接至氨基末端信号传导结构域的亲脂部分，并且羧基末端结构域充当分子内胆固醇转移酶。使用胆固醇来修饰胚胎信号蛋白可能解释了胆固醇生物合成紊乱对动物发育的一些影响。
Hedgehog (Hh) proteins comprise a family of secreted signaling molecules essential for patterning a variety of structures in animal embryogenesis. During biosynthesis, Hh undergoes an autocleavage reaction, mediated by its carboxyl-terminal domain, that produces a lipid-modified amino-terminal fragment responsible for all known Hh signaling activity. Here it is reported that cholesterol is the lipophilic moiety covalently attached to the amino-terminal signaling domain during autoprocessing and that the carboxyl-terminal domain acts as an intramolecular cholesterol transferase. This use of cholesterol to modify embryonic signaling proteins may account for some of the effects of perturbed cholesterol biosynthesis on animal development.