La autoantigen is cleaved in the COOH terminus and loses the nuclear localization signal during apoptosis

La autoantigen is a 47-kDa nuclear protein that binds to nascent polymerase III transcripts and a number of viral RNAs. We show that La protein was cl eaved to generate a 43-kDa fragment during apoptosis of human leukemic HL-6 0 cells treated with camptothecin or etoposide. Immunofluorescence microsco py showed that the La protein level was increased in the cytoplasm during a poptosis of HL-60 cells. In addition, UV irradiation of HeLa cells led to t he cleavage and redistribution of La protein upon apoptosis. Several lines of evidence show that La protein is cleaved by caspase-3 or closely related proteases at Asp-374 in the COOH terminus. When the full-length (La) and C OOH-terminally truncated (La Delta C374) forms of La protein were expressed as fusion proteins with green fluorescence protein (GFP), GFP-La Delta C37 4 was predominantly cytoplasmic, whereas GFP-La was localized in the nucleu s. These results suggest that La protein loses the nuclear localization sig nal residing in the COOH terminus upon cleavage and is thus redistributed t o the cytoplasm during apoptosis.