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Rapamycin inhibits didemnin B‐induced apoptosis in human HL‐60 cells: Evidence for the possible involvement of FK506‐binding protein 25
Author(s) -
Johnson Karina L,
Lawen Alfons
Publication year - 1999
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1046/j.1440-1711.1999.00821.x
Subject(s) - fkbp , kinase , apoptosis , microbiology and biotechnology , chemistry , protein kinase a , biology , biochemistry
In the present paper we show that the immunosuppressant rapamycin inhibits the induction of apoptosis by didemnin B in human promyeloid HL‐60 cells. The mechanism of this inhibition is investigated using FK506, which competes with rapamycin for binding to their common target FK506‐binding protein (FKBP)12. The lack of competition for rapamycin‐mediated inhibition of didemnin B‐induced apoptosis by FK506 suggests that rapamycin inhibits apoptosis through some mechanism other than inhibition of p70 S6 kinase activation. The lack of inhibition of didemnin B‐induced apoptosis by inhibitors of phosphatidylinositol 3‐kinase and mitogen‐activated protein (MAP) kinase kinase further supports the conclusion that rapamycin does not inhibit didemnin B‐induced apoptosis through inhibition of the MAP kinase pathway. Furthermore, didemnin B‐induced apoptosis is not inhibited by the inhibitors of cyclin‐dependent kinase, roscovitine and olomoucine. This indicates that rapamycin does not act through inhibition of cyclin‐dependent kinases. Together with the lack of competition for the effect of rapamycin by FK506, our data suggest the possible involvement of the FK506‐binding protein, FKBP25, which is localized in the nucleus. This interpretation of our data gains support from the fact that didemnin B does not induce apoptosis in enucleated HL‐60 cells, which supports the possible involvement of FKBP25 in the inhibition of apoptosis by rapamycin.