健康与疾病状态下磷酸肌醇3激酶表达的调控
Regulation of phosphoinositide 3-kinase expression in health and disease.
作者信息
Kok Klaartje, Geering Barbara, Vanhaesebroeck Bart
机构信息
Centre for Cell Signalling, Institute of Cancer, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1 M 6BQ, UK.
出版信息
Trends Biochem Sci. 2009 Mar;34(3):115-27. doi: 10.1016/j.tibs.2009.01.003. Epub 2009 Mar 18.
Both the biology and the therapeutic potential of the phosphoinositide 3-kinase (PI3K) signalling axis have been the subject of intense investigation; however, little is known about the regulation of PI3K expression. Emerging evidence indicates that PI3K levels change in response to cellular stimulation with insulin and nuclear receptor ligands, and during various physiological and pathological processes including differentiation, regeneration, hypertension and cancer. Recently identified mechanisms that control PI3K production include increased gene copy number in cancer, and transcriptional regulation of the p110alpha PI3K gene by FOXO3a, NF-kappaB and p53, and of the PI3K regulatory subunits by STAT3, EBNA-2 and SREBP. In most instances, however, the impact of alterations in PI3K expression on PI3K signalling and disease remains to be established.
磷酸肌醇3激酶（PI3K）信号轴的生物学特性和治疗潜力均已成为深入研究的对象；然而，关于PI3K表达的调控却知之甚少。新出现的证据表明，PI3K水平会随着胰岛素和核受体配体对细胞的刺激而变化，并且在包括分化、再生、高血压和癌症在内的各种生理和病理过程中也会发生变化。最近确定的控制PI3K产生的机制包括癌症中基因拷贝数的增加，以及FOXO3a、NF-κB和p53对p110α PI3K基因的转录调控，还有STAT3、EBNA-2和SREBP对PI3K调节亚基的转录调控。然而，在大多数情况下，PI3K表达改变对PI3K信号传导和疾病的影响仍有待确定。
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