tailieunhanh - báo cáo khoa hoc : New insights into the functions and localization of nuclear transglutaminase 2

Transglutaminase 2 (TG2; EC ) is the most abundantly expressed member of the transglutaminase family and exerts opposing effects on cell growth, differentiation and apoptosis via multiple activities, including transamidase, GTPase, cell adhesion, protein disulfide isomerase, kinase and scaffold activities. | IFEBS Journal MINIREVIEW New insights into the functions and localization of nuclear transglutaminase 2 Ting-Fang Kuo1 2 Hideki Tatsukawa1 and Soichi Kojima1 2 1 Molecular Ligand Biology Research Team ChemicalGenomics Research Group ChemicalBiology Department RIKEN Advanced Science Institute Wako Saitama Japan 2 Department of BiologicalSciences Graduate Schoolof Bioscience and Biotechnology Tokyo Institute of Technology Japan Keywords exportin importin nuclear localization nuclear TG2 regulation of gene expression Correspondence S. Kojima Molecular Ligand Biology Research Team Chemical Genomics Research Group Chemical Biology Department RIKEN Advanced Science Institute Wako Saitama 351-0198 Japan Fax 81 48 462 4675 Tel 81 48 467 7938 E-mail skojima@ Received 2 September 2011 revised 23 October 2011 accepted 25 October 2011 doi Transglutaminase 2 TG2 EC is the most abundantly expressed member of the transglutaminase family and exerts opposing effects on cell growth differentiation and apoptosis via multiple activities including transamidase GTPase cell adhesion protein disulfide isomerase kinase and scaffold activities. It is distributed in and around various parts of a cell including the extracellular matrix plasma membrane cytosol mitochondria and nucleus. Generally nuclear TG2 represents only 5-7 of the total TG2 in a cell and various stimuli will increase nuclear TG2 via cellular stress and or an increased intracellular Ca2 concentration. There is increasing evidence indicating the importance of nuclear TG2 in regulating gene expression via post-translational modification of or interaction with transcriptional factors and related proteins. These include E2F1 hypoxia inducible factor 1 Sp1 and histones. Through this mechanism TG2 controls cell growth or survival differentiation and apoptosis and is involved in the pathogenesis and or treatment of neurodegenerative diseases liver diseases and cancers. .