Intracellular localization and activity state of tissue transglutaminase differentially impacts cell death.

摘要: Tissue transglutaminase (tTG) is a unique member of the family as it both transamidating enzyme and GTPase. In cell tTG mostly cytosolic, however also found in nucleus associated with plasma membrane. can be proapoptotic, anti-apoptotic activities have been reported. To determine how intracellular localization activity modulates its effects on apoptosis, HEK293 cells were transiently transfected or [C277S]tTG (which lacks activity) constructs that targeted to different compartments. Apoptosis was induced by thapsigargin treatment, which results increased calcium concentrations. Cytosolic pro-apoptotic, while nuclear attenuated apoptosis. Membrane-targeted had neither pro- nor functions. This finding indicates for first time an important determinant effect Previous studies suggested may modulate retinoblastoma (Rb) protein, suppressor interacted Rb after induction interaction nuclear-targeted significantly concomitant attenuation contrast, decreased apoptosis not attenuated. These data suggest protects against response stimuli do result translocating nucleus, complexing aspect protective tTG.