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Cell cycle‐dependent caspase‐8 enzymatic activity is necessary for rapid lymphocyte proliferation
Author(s) -
Walsh Craig Michael,
Leverrier Sabrina
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.662.10
Subject(s) - caspase , apoptosis , caspase 8 , microbiology and biotechnology , caspase 3 , receptor , cell growth , programmed cell death , lymphocyte , caspase 2 , biology , cysteine protease , t cell , enzyme , protease , chemistry , biochemistry , immunology , immune system
Caspase‐8 is a cysteine protease recruited to ligated death receptors and is an essential intermediary in the generation of apoptotic signals. Caspase‐8 has also been found to be necessary for the clonal expansion of lymphocytes under certain mitogenic conditions. Consistent with this, caspase‐8 enzymatic activity was strongly induced in non‐apoptotic T cells, as assessed using a fluorogenic probe specific for caspase‐8. This enzymatic activation was found to be essential for efficient T cell proliferation, since caspase‐8 deficient T cell mitogenesis was rescued by enzymatically active, but not inactive caspase‐8 expressing retroviruses. The induction of caspase‐8 activity was found to be highest in proliferating CD8+ T cells or in B cells activated by lipopolysaccharide. While caspase‐8 activity did not depend on death receptors, it was dependent upon cell cycle progression, since inhibitors of various stages of the cell cycle afforded a graded blockade in caspase‐8 enzymatic activity. Although Fas ligation led to caspase‐8 autoproteolytic processing, proliferation‐induced caspase‐8 activation did not induce such processing. These results suggest that in rapidly dividing lymphocytes, caspase‐8 enzymatic activity is induced in a manner distinct from its activation by ligated death receptors and is required for rapid lymphocyte proliferation. This work was funded by an award from NIAID (R01AI50506).