Jl. Taupin et al., THE RNA-BINDING PROTEIN TIAR IS TRANSLOCATED FROM THE NUCLEUS TO THE CYTOPLASM DURING FAS-MEDIATED APOPTOTIC CELL-DEATH, Proceedings of the National Academy of Sciences of the United Statesof America, 92(5), 1995, pp. 1629-1633
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.