Gelb Michael H, Brunsveld Lucas, Hrycyna Christine A, Michaelis Susan, Tamanoi Fuyuhiko, Van Voorhis Wesley C, Waldmann Herbert
Department of Chemistry, University of Washington, Seattle, Washington 98195, USA.
Nat Chem Biol. 2006 Oct;2(10):518-28. doi: 10.1038/nchembio818.
In eukaryotic cells, a specific set of proteins are modified by C-terminal attachment of 15-carbon farnesyl groups or 20-carbon geranylgeranyl groups that function both as anchors for fixing proteins to membranes and as molecular handles for facilitating binding of these lipidated proteins to other proteins. Additional modification of these prenylated proteins includes C-terminal proteolysis and methylation, and attachment of a 16-carbon palmitoyl group; these modifications augment membrane anchoring and alter the dynamics of movement of proteins between different cellular membrane compartments. The enzymes in the protein prenylation pathway have been isolated and characterized. Blocking protein prenylation is proving to be therapeutically useful for the treatment of certain cancers, infection by protozoan parasites and the rare genetic disease Hutchinson-Gilford progeria syndrome.
在真核细胞中，一组特定的蛋白质会通过在其C末端连接15碳的法尼基基团或20碳的香叶基香叶基基团而被修饰，这些基团既作为将蛋白质固定到膜上的锚定物，又作为促进这些脂化蛋白质与其他蛋白质结合的分子柄。这些异戊二烯化蛋白质的进一步修饰包括C末端蛋白水解和甲基化，以及连接一个16碳的棕榈酰基团；这些修饰增强了膜锚定作用，并改变了蛋白质在不同细胞膜区室之间移动的动力学。蛋白质异戊二烯化途径中的酶已被分离和鉴定。事实证明，阻断蛋白质异戊二烯化在治疗某些癌症、原生动物寄生虫感染以及罕见的遗传性疾病哈钦森-吉尔福德早衰综合征方面具有治疗作用。
