NUCLEAR TRANSLOCATION OF TISSUE-TYPE TRANSGLUTAMINASE DURING SPHINGOSINE-INDUCED CELL-DEATH - A NOVEL ASPECT OF THE ENZYME WITH DNA HYDROLYTIC ACTIVITY

Tissue type (type 2) transglutaminase (TGase, EC 2.3.2.13) has been im plicated in various cellular processes including cell death. In order to better understand the role of this enzyme in cell death, human mela nocytic A375-S2 cells were treated with sphingosine, a cell-signaling mediator. During the rapid onset of cytotoxicity caused by this lipidi c agent, tissue TGase was translocated from the cytoplasm to the cell nuclei. This observation was further remarked in relevance to its prev iously undescribed activity for DNA degradation. The DNA hydrolytic ac tivity associated with tissue TGase was dependent on Mg2+ in contrast to the Ca2+ requirement for the classical cross-linking activity of TG ase, and was inhibited by Zn2+. Based on the results shown here, we pr opose a novel aspect of tissue TGase in cell death.