文章：

致癌PI3K调控转录和翻译

Oncogenic PI3K deregulates transcription and translation

原文发布日期：2005-12-01

DOI: 10.1038/nrc1753

类型: Review Article

开放获取: 否

要点：

1. Phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that generate second messengers that govern cellular activities and properties including proliferation, survival, motility and morphology.
2. PIK3CA, the gene that encodes the catalytic subunit p110a of PI3K, is frequently mutated in human solid tumours.
3. Cancer-specific mutations are clustered in the helical and the kinase domains of p110a. The amino-acid residues E542, E545 and H1047 are prominent mutational hot spots.
4. The mutations in the p110a hot spots induce a gain of enzymatic function and confer oncogenic activity both in vitro and in vivo.
5. The oncogenicity of PI3K is the result of interactions with transcriptional and translational controls.

要点翻译：

1. 磷脂酰肌醇3-激酶（PI3Ks）是一类能够生成第二信使的脂质激酶，这些信使调控着细胞的活动与特性，包括增殖、存活、运动及形态。
2. PIK3CA基因编码PI3K的催化亚基p110α，该基因在人类实体瘤中频繁发生突变。
3. 癌症特异性突变集中分布于p110α的螺旋结构域和激酶结构域，其中E542、E545和H1047氨基酸残基是显著的突变热点。
4. p110α热点突变可增强酶功能活性，并在体外及体内实验中均展现出致癌特性。
5. PI3K的致癌性源于其与转录及翻译调控机制的相互作用。

英文摘要：

There have long been indications of a role for PI3K (phosphatidylinositol 3-kinase) in cancer pathogenesis. Experimental data document a requirement for deregulation of both transcription and translation in PI3K-mediated oncogenic transformation. The recent discoveries of cancer-specific mutations in PIK3CA, the gene that encodes the catalytic subunit p110α of PI3K, have heightened the interest in the oncogenic potential of this lipid kinase and have made p110α an ideal drug target.

摘要翻译： 

长期以来，研究提示PI3K（磷脂酰肌醇3-激酶）在癌症发病机制中发挥作用。实验数据表明，在PI3K介导的致癌转化过程中，转录和翻译的失调都是必需的。近期发现编码PI3K催化亚基p110α的基因PIK3CA存在癌症特异性突变，这进一步激发了人们对该脂质激酶致癌潜力的兴趣，并使p110α成为理想的药物靶点。

原文链接：

Oncogenic PI3K deregulates transcription and translation