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 implicated in various cellular processes including cell death. In order to better understand the role of this enzyme in cell death, human melanocytic A375-S2 cells were treated with sphingosine, a cell-signaling mediator. During the rapid onset of cytotoxicity caused by this lipidic agent, tissue TGase was translocated from the cytoplasm to the cell nuclei. This observation was further remarked in relevance to its previously undescribed activity for DNA degradation. The DNA hydrolytic activity associated with tissue TGase was dependent on Mg2+ in contrast to the Ca2+ requirement for the classical cross-linking activity of TGase, and was inhibited by Zn2+. Based on the results shown here, we propose a novel aspect of tissue TGase in cell death.