Aminoacyl-tRNA synthetase-interacting multi-functional protein 1/p43: an emerging therapeutic protein working at systems level

作者：Lee Sang Won; Kim Gyuyoup; Kimt Sunghoon^*

来源：Expert Opinion on Drug Discovery, 2008, 3(8): 945-957.

DOI：10.1517/17460440802256905

• aminoacyl-tRNA synthetases
• ARS-interacting multi-functional proteins
• multiple phenotypes
• multi-tRNA synthetase complex
• therapeutic proteins
• systems biology

Background: Drug discovery programs are based on the presumption of one drug-one action-one disease, which is frustrated by the complexity of biological systems. Because the aberration of a single gene often leads to multiple pathological symptoms, we should understand the functional network of the disease-related proteins to develop effective therapy. Objectives: To describe how activities of proteins are reflected in phenotypes and their pathological implications using aminoacyl-tRNA synthetase-interacting multi-functional protein 1 (AIMP1). Methods: The physiological activities of AIMP1 are unveiled through in vitro approaches and in vivo phenotyptic investigation. Bioinformatics tool was used to combine all AIMP1-target proteins. Conclusion: Although a cytosolic protein, AIMP1 can be secreted as a cytokine to control immune response, angiogenesis and wound healing, and as a glucagon-like hormone for glucose homeostasis. It is involved in the regulation of autoimmune control and TGF-beta signaling within the cells. AIMP1-deficient mice developed multiple phenotypes in immune systems, metabolism and body growth. The therapeutic potential of this multi-functional protein with associated biological activities are discussed.

• 出版日期2008-8