Abstract

Keywords

Nuclear translocation of granzyme B in target cell apoptosis

MJ Pinkoski^1,2, JA Heibein¹, M Barry¹ & RC Bleackley¹

Correspondence to: RC Bleackley, Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada, T6G 2H7. Tel: (780) 492-3968; Fax: (780) 492-0886; E-mail: chris.bleackley@ualberta.ca

Edited by C Thiele

Granzyme B is the prototypic member of a family of serine proteases localized to the cytolytic granules of cytotoxic lymphocytes. Together with another 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, we showed that granzyme B binds to a nuclear protein in a manner dependent on its enzymatic activity. Here, we demonstrate that granzyme B is translocated rapidly to the nucleus in cells that have been induced to undergo apoptosis by a granzyme-dependent process, and that translocation is dependent on caspase activity. Appearance of granzyme B in the nucleus of target cells precedes the detection of DNA fragmentation. Although not directly responsible for DNA fragmentation, these data suggest a nuclear role for granzyme B in target cell apoptosis. c-Abl nuclear functions. Cell Death and Differentiation (2000) 7, 17 – 24.

^© Macmillan Publishers Ltd 2000