Nuclear translocation of a leukocyte elastase inhibitor/elastase complex during staurosporine-induced apoptosis: Role in the generation of nuclear L-DNase II activity

Using L1210 murine leukemia cells, we have previously shown that in respons e to treatment with drugs having different targets, apoptotic cell death oc curs through at least two different signaling pathways. Here, we present ev idence that nuclear extracts from staurosporine-treated cells elicit DNase II activity that is not detected in nuclear extracts from cisplatin-treated cells. This activity correlates with the accumulation of two nuclear prote ins (70 and 30 kDa) which are detected by an anti-L-DNase II antibody. Part ial purification of this DNase II activity suggests that the 30-kDa protein could be the nuclease responsible for staurosporine-induced DNA fragmentat ion. The 70-kDa protein is also recognized by an anti-elastase antibody, su ggesting that it carries residues belonging to both L-DNase II and elastase , Since previous findings showed that L-DNase II was generated from the leu kocyte inhibitor of elastase, we propose that the 70-kDa protein results fr om an SDS-stable association between these two proteins and is translocated from the cytoplasm to the nucleus during staurosporine-induced apoptosis. (C) 2000 Academic Press.