Stabilization of Cyclin-Dependent Kinase 4 by Methionyl-tRNA Synthetase in p16INK4a-Negative Cancer.

Although abnormal increases in the level or activity of cyclin-dependent kinase 4 (CDK4) occur frequently in cancer, the underlying mechanism is not fully understood. Here, we show that methionyl-tRNA synthetase (MRS) specifically stabilizes CDK4 by enhancing the formation of the complex between CDK4 and a chaperone protein. Knockdown of MRS reduced the CDK4 level, resulting in G0/G1 cell cycle arrest. The effects of MRS on CDK4 stability were more prominent in the tumor suppressor p16INK4a-negative cancer cells because of the competitive relationship of the two proteins for binding to CDK4. Suppression of MRS reduced cell transformation and the tumorigenic ability of a p16INK4a-negative breast cancer cell line in vivo. Further, the MRS levels showed a positive correlation with those of CDK4 and the downstream signals at high frequency in p16INK4a-negative human breast cancer tissues. This work revealed an unexpected functional connection between the two enzymes involving protein synthesis and the cell cycle.

Simulation for Large-Area, Inductively-Coupled Plasma Systems Using an Ar/Cl2 Gas Mixture.

As research and development of high-performance devices are becoming increasingly important in the flat panel display industry, new structures and processes are essential to improve the performance of the TFT backplane. Also, high-density plasma systems are needed for new device fabrications. Chlorine-based, inductively-coupled plasma systems are widely used for highly-selective, anisotropic etching of polysilicon layers. In this paper, a plasma simulation for a large-area ICP system (8th glass size and 9 planar antenna set) was conducted using Ar/Cl2 gas. Transport models and Maxwell Equations were applied to calculate the plasma parameters such as electron density, electron temperature and electric potential. In addition, the spatial distribution of ions such as Ar+, Cl2+, Cl-, Cl+ were investigated respectively.

Increased production of reactive oxygen species by the vacuolar-type (H(+))-ATPase inhibitors bafilomycin A1 and concanamycin A in RAW 264 cells.

Treatment of the mouse leukemic cell line RAW 264 with bafilomycin A1 or concanamycin A, inhibitors of vacuolar-type (H(+))-ATPases (V-ATPases), significantly increased the production of reactive oxygen species (ROS) and decreased cell viability. These effects were significantly suppressed by the presence of N-acetyl cysteine (NAC), an ROS scavenger. si-RNA mediated knockdown of the gene for the c subunit of the V0 domain of V-ATPase also resulted in an increase in ROS production and a decrease in cell viability. These results suggest that decreased cellular V-ATPase activity decreases cell viability by increasing ROS production in RAW 264 cells.