Nuclear translocation of granzyme B in target cell apoptosis

Granzyme B is the prototypic member of a family of serine proteases localiz ed to the cytolytic granules of cytotoxic lymphocytes. Together with anothe r granule protein, perforin, granzyme B is capable of inducing all aspects of apoptotic death in target cells. A number of granzyme B substrates have been identified and it has been demonstrated that granzyme B is responsible , directly or indirectly, for the morphological nuclear changes observed in target cell apoptosis, including DNA fragmentation. In an earlier study, w e showed that granzyme B binds to a nuclear protein in a manner dependent o n its enzymatic activity. Here, we demonstrate that granzyme B is transloca ted rapidly to the nucleus in cells that have been induced to undergo apopt osis by a granzyme-dependent process, and that translocation is dependent o n caspase activity. Appearance of granzyme B in the nucleus of target cells precedes the detection of DNA fragmentation. Although not directly respons ible for DNA fragmentation, these data suggest a nuclear role for granzyme B in target cell apoptosis. c-Abl nuclear functions.