PIP4K and the role of nuclear phosphoinositides in tumour suppression

被引：46

作者：

Fiume, Roberta ^{[1
]}

Stijf-Bultsma, Yvette ^{[2
]}

Shah, Zahid H. ^{[2
]}

Keune, Willem Jan ^{[3
]}

Jones, David R. ^{[4
]}

Jude, Julian Georg ^{[5
]}

Divecha, Nullin ^{[2
]}

机构：

[1] Univ Bologna, DIBINEM, Cellular Signalling Lab, Bologna, Italy

[2] Univ Southampton, Fac Nat & Environm Sci, Ctr Biol Sci, Inositide Lab, Southampton SO17 1BJ, Hants, England

[3] Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands

[4] AstraZeneca, Oncol iMED, Macclesfield SK10 4TF, Cheshire, England

[5] IMP, A-1030 Vienna, Austria

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS | 2015年 / 1851卷 / 06期

关键词：

PIP4K; PHOSPHATIDYLINOSITOL; 5-PHOSPHATE; 4-KINASE; PROTEIN-KINASE-C; PHOSPHATE KINASE; PHOSPHOLIPASE-C; DNA METHYLATION; PHD FINGER; E-CADHERIN; II-BETA; OXIDATIVE STRESS; INOSITOL LIPIDS;

D O I：

10.1016/j.bbalip.2015.02.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Phosphatidylinositol-5-phosphate (PtdIns5P)-4-kinases (PIP4Ks) are stress-regulated lipid kinases that phosphorylate PtdIns5P to generate PtdIns(4,5)P-2. 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. (C) 2015 Elsevier B.V. All rights reserved.

引用

页码：898 / 910

页数：13

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[1] Inositol hexakisphosphate and Gle1 activate the DEAD-box protein Dbp5 for nuclear mRNA export [J].