[Abstract] 

Cancer cells need many building blocks to continuously proliferate and migrate. Glucose availability is one of the most important factors that determines cell growth and death. Amino acid signal transduction pathway is considered as a pivotal cascade to understand cell growth and proliferation since mammalian target of rapamycin (mTOR) was identified as a central regulator of cellular metabolism. Despite the importance of glucose or amino acid starvation responses, controlling mechanisms for metabolic changes under nutrients starvation has not been well understood. Here we show that leucyl-tRNA synthetase (LARS), one of aminoacyltRNA synthetases (ARSs), plays a crucial role in metabolic shift of amino acid usage from protein synthesis to energy production. LARS was previously shown to serve as amino acid

sensor for mTOR pathway that is frequently up-regulated in many cancers. We also have synthesized diverse chemical series with different mode of action and tested how they would affect the cellular protein synthesis as well as the catalytic activity of LARS. In this talks, we will present this story in detail.