PIP4K and the role of nuclear phosphoinositides in tumour suppression.

Autor:	Fiume R; Cellular Signalling Laboratory, DIBINEM, University of Bologna, Bologna, Italy. Electronic address: roberta.fiume@unibo.it., Stijf-Bultsma Y; Inositide Laboratory, Centre for Biological Sciences, Faculty of Natural & Environmental Sciences, Life Sciences Building 85, University of Southampton, Highfield Campus, Southampton SO17 1BJ, UK., Shah ZH; Inositide Laboratory, Centre for Biological Sciences, Faculty of Natural & Environmental Sciences, Life Sciences Building 85, University of Southampton, Highfield Campus, Southampton SO17 1BJ, UK., Keune WJ; The Netherlands Cancer Institute, Amsterdam 1066CX, The Netherlands., Jones DR; Oncology iMED, AstraZeneca, Alderley Park, Macclesfield SK10 4TF, UK., Jude JG; IMP - Institute of Molecular Pathology, Vienna Biocenter, Dr. Bohr-Gasse 7, 1030 Vienna, Austria., Divecha N; Inositide Laboratory, Centre for Biological Sciences, Faculty of Natural & Environmental Sciences, Life Sciences Building 85, University of Southampton, Highfield Campus, Southampton SO17 1BJ, UK. Electronic address: N.Divecha@soton.ac.uk.
Jazyk:	angličtina
Zdroj:	Biochimica et biophysica acta [Biochim Biophys Acta] 2015 Jun; Vol. 1851 (6), pp. 898-910. Date of Electronic Publication: 2015 Feb 26.
DOI:	10.1016/j.bbalip.2015.02.014
Abstrakt:	Phosphatidylinositol-5-phosphate (PtdIns5P)-4-kinases (PIP4Ks) are stress-regulated lipid kinases that phosphorylate PtdIns5P to generate PtdIns(4,5)P₂. There are three isoforms of PIP4Ks: PIP4K2A, 2B and 2C, which localise to different subcellular compartments with the PIP4K2B isoform being localised predominantly in the nucleus. Suppression of PIP4K expression selectively prevents tumour cell growth in vitro and prevents tumour development in mice that have lost the tumour suppressor p53. p53 is lost or mutated in over 70% of all human tumours. These studies suggest that inhibition of PIP4K signalling constitutes a novel anti-cancer therapeutic target. In this review we will discuss the role of PIP4K in tumour suppression and speculate on how PIP4K modulates nuclear phosphoinositides (PPIns) and how this might impact on nuclear functions to regulate cell growth. This article is part of a Special Issue entitled Phosphoinositides. (Copyright © 2015 Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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