Regulation of phosphoinositide 3-kinase expression in health and disease
Klaartje Kok1, Barbara Geering, Bart Vanhaesebroeck
1Centre 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.
Abstract:
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.
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