Targeting protein lipidation in disease

被引:106
作者
Resh, Marilyn D. [1 ]
机构
[1] Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10065 USA
基金
美国国家卫生研究院;
关键词
GERANYLGERANYLTRANSFERASE-I INHIBITORS; MEMBRANE-BINDING; SONIC HEDGEHOG; RAS LOCALIZATION; WNT PROTEINS; S-ACYLATION; H-RAS; PALMITOYLATION; FARNESYLTRANSFERASE; SRC;
D O I
10.1016/j.molmed.2012.01.007
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Fatty acids and/or isoprenoids are covalently attached to a variety of disease-related proteins. The distinct chemical properties of each of these hydrophobic moieties allow lipid modification to serve as a mechanism to regulate protein structure, localization and function. This review highlights recent progress in identifying inhibitors of protein lipidation and their effects on human disease. Myristoylation inhibitors have shown promise in blocking the action of human pathogens. Although inhibitors that block prenylation of Ras proteins have not yet been successful for cancer treatment, they may be efficacious in the rare premature aging syndrome progeria. Agents that alter the palmitoylation status of Ras, Wnt and Hh proteins have recently been discovered, and represent the next generation of potential chemotherapeutics.
引用
收藏
页码:206 / 214
页数:9
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