Genetic and Epigenetic Regulation of Phosphoinositide 3-kinase Isoforms

被引：7
作者：
Fyffe, Chanse [1 ]
Buus, Richard [1 ]
Falasca, Marco [1 ]
机构：
[1] Queen Mary Univ London, Barts & London Sch Med & Dent, Inositide Signalling Grp, Ctr Diabet,Blizard Inst, London E1 2AT, England
来源：
CURRENT PHARMACEUTICAL DESIGN | 2013年 / 19卷 / 04期
关键词：
PI3K; genetic; epigenetic; cancer; SNP; mutations; regulation; PROTEIN-KINASE-B; PHOSPHATIDYLINOSITOL; 3-KINASE; CELL-PROLIFERATION; HIGH-FREQUENCY; PIK3CA GENE; SELECTIVE INHIBITOR; P110-ALPHA ISOFORM; DIFFERENTIAL ROLES; CATALYTIC SUBUNIT; GLUCOSE-TRANSPORT;
D O I：
10.2174/138161213804581873
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
The last quarter of a century has witnessed remarkable progress in the understanding of phosphoinositide 3-kinases (PI3K) signalling and their involvement in different diseases such as cancer, diabetes and inflammation. Nevertheless, many questions remain open and among these the role of genetic and epigenetic regulation of PI3K isoforms is one of the most prominent. Emerging evidence Indicates that levels of isoforms can be modulated upon stimulation or in both physiological and pathological conditions including increased gene copy number and transcription regulation. In addition, an intriguing role for epigenetic regulation of PI3K expression, caused by mechanisms other than changes in the underlying DNA sequence, are starting to get appreciated. In this review, we summarize the genetic and epigenetic regulation of PI3Ks in physiology and the role played by their alterations in different diseases.
引用
收藏
页码：680 / 686
页数：7
相关论文
共 113 条
[1]   Transduction of interleukin-2 antiapoptotic and proliferative signals via Akt protein kinase [J].
Ahmed, NN ;
Grimes, HL ;
Bellacosa, A ;
Chan, TO ;
Tsichlis, PN .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (08) :3627-3632
[2]   Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase B alpha [J].
Alessi, DR ;
James, SR ;
Downes, CP ;
Holmes, AB ;
Gaffney, PRJ ;
Reese, CB ;
Cohen, P .
CURRENT BIOLOGY, 1997, 7 (04) :261-269
[3]   Essential role for the p110δ phosphoinositide 3-kinase in the allergic response [J].
Ali, K ;
Bilancio, A ;
Thomas, M ;
Pearce, W ;
Gilfillan, AM ;
Tkaczyk, C ;
Kuehn, N ;
Gray, A ;
Giddings, J ;
Peskett, E ;
Fox, R ;
Bruce, I ;
Walker, C ;
Sawyer, C ;
Okkenhaug, K ;
Finan, P ;
Vanhaesebroeck, B .
NATURE, 2004, 431 (7011) :1007-1011
[4]   Mechanisms underlying p53 regulation of PIK3CA transcription in ovarian surface epithelium and in ovarian cancer [J].
Astanehe, Arezoo ;
Arenillas, David ;
Wasserman, Wyeth W. ;
Leung, Peter C. K. ;
Dunn, Sandra E. ;
Davies, Barry R. ;
Mills, Gordon B. ;
Auersperg, Nelly .
JOURNAL OF CELL SCIENCE, 2008, 121 (05) :664-674
[5]   The PIK3CA gene is mutated with high frequency in human breast cancers [J].
Bachman, KE ;
Argani, P ;
Samuels, Y ;
Silliman, N ;
Ptak, J ;
Szabo, S ;
Konishi, H ;
Karakas, B ;
Blair, BG ;
Lin, C ;
Peters, BA ;
Velculescu, VE ;
Park, BH .
CANCER BIOLOGY & THERAPY, 2004, 3 (08) :772-775
[6]   The regulation and function of Class III PI3Ks: novel roles for Vps34 [J].
Backer, Jonathan M. .
BIOCHEMICAL JOURNAL, 2008, 410 (01) :1-17
[7]   Both p110α and p110β isoforms of PI3K can modulate the impact of loss-of-function of the PTEN tumour suppressor [J].
Berenjeno, Inma M. ;
Guillermet-Guibert, Julie ;
Pearce, Wayne ;
Gray, Alexander ;
Fleming, Stewart ;
Vanhaesebroeck, Bart .
BIOCHEMICAL JOURNAL, 2012, 442 :151-159
[8]   A selective inhibitor of the p110δ isoform of PI 3-kinase inhibits AML cell proliferation and survival and increases the cytotoxic effects of VP16 [J].
Billottet, C. ;
Grandage, V. L. ;
Gale, R. E. ;
Quattropani, A. ;
Rommel, C. ;
Vanhaesebroeck, B. ;
Khwaja, A. .
ONCOGENE, 2006, 25 (50) :6648-6659
[9]   Differential roles for the p101 and p84 regulatory subunits of PI3Kγ in tumor growth and metastasis [J].
Brazzatti, J. A. ;
Klingler-Hoffmann, M. ;
Haylock-Jacobs, S. ;
Harata-Lee, Y. ;
Niu, M. ;
Higgins, M. D. ;
Kochetkova, M. ;
Hoffmann, P. ;
McColl, S. R. .
ONCOGENE, 2012, 31 (18) :2350-2361
[10]   PROTEIN-KINASE-B (C-AKT) IN PHOSPHATIDYLINOSITOL-3-OH INASE SIGNAL-TRANSDUCTION [J].
BURGERING, BMT ;
COFFER, PJ .
NATURE, 1995, 376 (6541) :599-602
12345678910