THE RNA-BINDING PROTEIN TIAR IS TRANSLOCATED FROM THE NUCLEUS TO THE CYTOPLASM DURING FAS-MEDIATED APOPTOTIC CELL-DEATH

We have determined the structure, intracellular localization, and tiss ue distribution of TIAR, a TIA-1-related RNA-binding protein. Two rela ted isoforms of TIAR, migrating at 42 and 50 kDa, are expressed in pri mate cells, Unlike TIA-I, which is found in the granules of cytotoxic lymphocytes, TIAR is concentrated in the nucleus of hematopoietic and nonhematopoietic cells, Because TIAR can trigger DNA fragmentation in permeabilized thymocytes, it is a candidate effector of apoptotic cell death. Consistent with this possibility, we have found that the expre ssion and intracellular localization of TIAR change dramatically durin g Fas-mediated apoptosis, TIAR moves from the nucleus to the cytoplasm within 30 min of Fas ligation. Redistribution of TIAR precedes the on set of DNA fragmentation and is not a nonspecific consequence of nucle ar disintegration, Cytoplasmic redistribution of TIAR is mot observed during cellular activation triggered by mitogens such as concanavalin A or phytohemagglutinin, Our results suggest that cytoplasmic redistri bution of TIAR may be a general feature of the apoptotic program.