tailieunhanh - Báo cáo khoa học: Mammalian transglutaminases Identification of substrates as a key to physiological function and physiopathological relevance

Transglutaminases form a large family of intracellular and extracellular enzymes that catalyse the Ca 2+ -dependent post-translational modification of proteins. Despite significant advances in our understanding of the biolo-gical role of most mammalian transglutaminase isoforms, recent findings suggest new scenarios, most notably for the ubiquitous tissue transglutami-nase. It is becoming apparent that some transglutaminases, normally expressed at low levels in many tissue types, are activated and⁄or over-expressed in a variety of diseases, thereby resulting in enhanced concentra-tions of cross-linked proteins. . | FEBS Journal REVIEW ARTICLE Mammalian transglutaminases Identification of substrates as a key to physiological function and physiopathological relevance Carla Esposito and Ivana Caputo Department of Chemistry University of Salerno Italy Keywords post-translationalmodification protein substrates proteomics transglutaminase Correspondence C. Esposito Department of Chemistry University of Salerno Via S. Allende 84081 Baronissi Salerno Italy Fax 39 089 965296 Tel 39 089 965298 E-mail cesposito@ Received 27 July 2004 revised 3 November 2004 accepted 10 November 2004 doi Transglutaminases form a large family of intracellular and extracellular enzymes that catalyse the Ca2 -dependent post-translational modification of proteins. Despite significant advances in our understanding of the biological role of most mammalian transglutaminase isoforms recent findings suggest new scenarios most notably for the ubiquitous tissue transglutaminase. It is becoming apparent that some transglutaminases normally expressed at low levels in many tissue types are activated and or overexpressed in a variety of diseases thereby resulting in enhanced concentrations of cross-linked proteins. As applies to all enzymes that exert their metabolic function by modifying the properties of target proteins the identification and characterization of the modified proteins will cast light on the functions of transglutaminases and their involvement in human diseases. In this paper we review data on the properties of mammalian transglutaminases particularly as regards their protein substrates and the relevance of transglutaminase-catalysed reactions in physiological and disease conditions. Mammalian transglutaminases and their catalytic activity Transglutaminases TGs EC are encoded by a family of structurally and functionally related genes. Nine TG genes have been identified eight of which encode active enzymes 1 . Only six TG enzymes have been isolated and

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