Nuclear translocation of granzyme B in target cell apoptosis.
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.
Pinkoski
M J
MJ
Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada, T6G 2H7.
Heibein
J A
JA
Barry
M
M
Bleackley
R C
RC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport; D019556:COS Cells; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D053938:DNA Fragmentation; D004789:Enzyme Activation; D053804:Granzymes; D006801:Humans; D019169:Jurkat Cells; D012697:Serine Endopeptidases / Q000378:metabolism*
C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases