Porter J A, Young K E, Beachy P A
Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Science. 1996 Oct 11;274(5285):255-9. doi: 10.1126/science.274.5285.255.
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.
刺猬（Hh）蛋白是一类分泌型信号分子家族，对于动物胚胎发育过程中多种结构的模式形成至关重要。在生物合成过程中，Hh会经历一种由其羧基末端结构域介导的自切割反应，产生一个脂质修饰的氨基末端片段，该片段负责所有已知的Hh信号活性。本文报道，胆固醇是在自加工过程中与氨基末端信号结构域共价连接的亲脂性部分，并且羧基末端结构域充当分子内胆固醇转移酶。这种利用胆固醇修饰胚胎信号蛋白的方式可能解释了胆固醇生物合成紊乱对动物发育的一些影响。
