IRS 1 promotes Competing interests The authors declare no potential conflict of interests. Authors contributions Dr. Shih Hung Chan conceived this study and conducted experiments. Dr. Hidenori Matsuzaki afforded sellectchem great help in the experiments. Prof. Jyh Hong Chen participated in the coordination of the study. Prof. Ushio Kikkawa helped to revise the manuscript. Prof. Wen Chang Chang conceived the study and critically revised the manuscript. All authors read and approved the final manuscript. Acknowledgments We thank Prof. Noboru Mizushima for the gift of GFP LC3 plasmids, and Miss Min Li Wu for her assistance in laboratory work. This work was supported by grants from National Cheng Kung University Hospital and from the Multidisciplinary Center of Inhibitors,Modulators,Libraries Excellence for Clinical Trial and Research cell growth and inhibits autophagy by enhancing mTOR activity.

it also promotes cell proliferation via activation of ERK signaling. ROS activates AMPK by activating ATM protein, or via other pathways. AMPK Inhibitors,Modulators,Libraries then pro motes autophagy through direct inhibition of mTOR, or by indirect inhibition of IRS 1AktmTOR signaling. By contrast, IRS 1 can reduce AMPK activity by inhibition of LKB1. Both the ERK and p70 S6K signal Inhibitors,Modulators,Libraries ing can induce autophagy. Conclusion Our results imply that IRS 1 plays a poorly defined but important role in the pathogenesis of human diseases that exhibit abnormal proliferation of cells, such as can cers, benign prostate hyperplasia, and atherosclerotic coronary artery disease. This is because IRS 1 can pro mote cell proliferation and help cells to resist the oxida tive stresses generated during cell proliferation.

Further investigation into the role of the IRS 1 protein in spe cific human diseases that feature increased expression levels of IRS 1 would be worthwhile. Genetic or pharmacologic intervention to inhibit IRS 1 signaling might be an effective strategy to treat diseases character ized by uncontrolled proliferation Inhibitors,Modulators,Libraries of cells. Abbreviations IRS Insulin receptor substrate. ROS Reactive oxygen species. GO Glucose oxidase. Inhibitors,Modulators,Libraries LC3 Microtubule associated protein 1 light chain 3. mTOR Mammalian target of rapamycin. p70 S6K p70 ribosomal protein S6 kinase. PI3K Phosphatidylinositol 3 kinase. AktPKB Protein kinase B. MAPK Mitogen activated protein kinase. ERK Extracellular signal regulated kinase. AMPK AMP activated protein kinase.

ATM Ataxia telangiectasia mutated. LKB Liver kinase B. DMEM Dulbeccos modified Eagle medium. ATG 5 Autophagy related gene 5. GFP Green fluorescence protein. PBS Phosphate buffered saline. TBS Tris buffered saline. PI Propidium iodide. EBSS Earles Balanced Salt Solution. ULK Unc 51 like kinase. FBS Fetal selleckchem bovine serum. shRNA Short hairpin RNA. DMSO Dimethyl sulfoxide. GSK Glycogen synthase kinase. Background A high incidence of atherosclerosis and thrombotic com plications has been associated with hypercholester olemia.