siRNA screening reveals JNK2 as an evolutionary conserved regulator of triglyceride homeostasis.
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.
Grimard
Vinciane
V
Max-Planck-Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Massier
Julia
J
Richter
Doris
D
Schwudke
Dominik
D
Kalaidzidis
Yannis
Y
Fava
Eugenio
E
Hermetter
Albin
A
Thiele
Christoph
C
D017124:Conserved Sequence / Q000502:physiology; D019143:Evolution, Molecular; D006367:HeLa Cells; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology; D048056:Mitogen-Activated Protein Kinase 9 / Q000235:genetics / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference / Q000502:physiology; D034741:RNA, Small Interfering / Q000502:physiology*; D012568:Schizosaccharomyces / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014280:Triglycerides / Q000378:metabolism*
D034741:RNA, Small Interfering; D029702:Schizosaccharomyces pombe Proteins; D014280:Triglycerides; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases; C095409:sty1 protein, S pombe