siRNA screening reveals JNK2 as an evolutionary conserved regulator of triglyceride homeostasis

被引:14
作者
Grimard, Vinciane [1 ]
Massier, Julia [1 ]
Richter, Doris [1 ]
Schwudke, Dominik [1 ]
Kalaidzidis, Yannis [1 ]
Fava, Eugenio [1 ]
Hermetter, Albin [2 ]
Thiele, Christoph [1 ]
机构
[1] Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany
[2] Graz Univ Technol, Inst Biochem, A-8010 Graz, Austria
关键词
c-jun N-terminal kinase; HeLa cells; kinase; lipid droplet; mitogen-activated protein kinase-9;
D O I
10.1194/jlr.M800168-JLR200
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
Lipid homeostasis is essential for proper function of cells and organisms. To unravel new regulators of this system, we developed a screening procedure, combining RNA interference in HeLa cells and TLC, which enabled us to monitor modifications of lipid composition resulting from short, interfering RNA knock-downs. We applied this technique to the analysis of 600 human kinases. Despite the occurrence of off-target effects, we identified JNK2 as a new player in triglyceride (TG) homeostasis and lipid droplet metabolism and, more specifically, in the regulation of lipolysis. Similar control of the level of TGs and lipid droplets was observed for its Schizosaccharomyces pombe homolog, Sty1, suggesting an evolutionary conserved function of mitogen-activated protein kinases in the regulation of lipid storage in eukaryotic cells.
引用
收藏
页码:2427 / 2440
页数:14
相关论文
共 61 条
[1]   PLD1 and ERK2 regulate cytosolic lipid droplet formation [J].
Andersson, Linda ;
Bostrom, Pontus ;
Ericson, Johanna ;
Rutberg, Mikael ;
Magnusson, Bjorn ;
Marchesan, Denis ;
Ruiz, Michel ;
Asp, Lennart ;
Huang, Ping ;
Frohman, Michael A. ;
Boren, Jan ;
Olofsson, Sven-Olof .
JOURNAL OF CELL SCIENCE, 2006, 119 (11) :2246-2257
[2]   Nuclear receptors in lipid metabolism: Targeting the heart of dyslipidemia [J].
Beaven, SW ;
Tontonoz, P .
ANNUAL REVIEW OF MEDICINE, 2006, 57 :313-329
[3]   SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase [J].
Bennett, BL ;
Sasaki, DT ;
Murray, BW ;
O'Leary, EC ;
Sakata, ST ;
Xu, WM ;
Leisten, JC ;
Motiwala, A ;
Pierce, S ;
Satoh, Y ;
Bhagwat, SS ;
Manning, AM ;
Anderson, DW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (24) :13681-13686
[4]   3′ UTR seed matches, but not overall identity, are associated with RNAi off-targets [J].
Birmingham, A ;
Anderson, EM ;
Reynolds, A ;
Ilsley-Tyree, D ;
Leake, D ;
Fedorov, Y ;
Baskerville, S ;
Maksimova, E ;
Robinson, K ;
Karpilow, J ;
Marshall, WS ;
Khvorova, A .
NATURE METHODS, 2006, 3 (03) :199-204
[5]   Lipid droplets: Proteins floating on a pool of fat [J].
Brown, DA .
CURRENT BIOLOGY, 2001, 11 (11) :R446-R449
[6]   A nutrition paradox - Uderweight and obesity in developing countries [J].
Caballero, B .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 352 (15) :1514-1516
[7]   Systematic genome-wide screens of gene function [J].
Carpenter, AE ;
Sabatini, DM .
NATURE REVIEWS GENETICS, 2004, 5 (01) :11-22
[8]   Nuclear receptors and lipid physiology: Opening the X-files [J].
Chawla, A ;
Repa, JJ ;
Evans, RM ;
Mangelsdorf, DJ .
SCIENCE, 2001, 294 (5548) :1866-1870
[9]   Global transcriptional responses of fission yeast to environmental stress [J].
Chen, DR ;
Toone, WM ;
Mata, J ;
Lyne, R ;
Burns, G ;
Kivinen, K ;
Brazma, A ;
Jones, N ;
Bähler, J .
MOLECULAR BIOLOGY OF THE CELL, 2003, 14 (01) :214-229
[10]  
Degols G, 1996, MOL CELL BIOL, V16, P2870