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Cited by 487

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

Caspase-3 Is the Primary Activator of Apoptotic DNA Fragmentation via DNA Fragmentation Factor-45/Inhibitor of Caspase-activated DNase Inactivation

Open access
Wolf, Beni B., Schuler, Martin, Echeverri, Fernando, Green, Douglas R.·1999·Journal of Biological Chemistry

Abstract

Caspase-3 initiates apoptotic DNA fragmentation by proteolytically inactivating DFF45 (DNA fragmentation factor-45)/ICAD (inhibitor of caspase-activated DNase), which releases active DFF40/CAD (caspase-activated DNase), the inhibitor's associated endonuclease. Here, we examined whether other apoptotic proteinases initiated DNA fragmentation via DFF45/ICAD inactivation. In a cell-free assay, caspases-3, -6, -7, -8, and granzyme B initiated benzoyloxycarbonyl-Asp-Glu-Val-Asp (DEVD) cleaving caspase activity, DFF45/ICAD inactivation, and DNA fragmentation, but calpain and cathepsin D failed to initiate these events. Strikingly, only the DEVD cleaving caspases, caspase-3 and caspase-7, inactivated DFF45/ICAD and promoted DNA fragmentation in an in vitro DFF40/CAD assay, suggesting that granzyme B, caspase-6, and caspase-8 promote DFF45/ICAD inactivation and DNA fragmentation indirectly by activating caspase-3 and/or caspase-7. In vitro, however, caspase-3 inactivated DFF45/ICAD and promoted DNA fragmentation more effectively than caspase-7 and endogenous levels of caspase-7 failed to inactivate DFF45/ICAD in caspase-3 null MCF7 cells and extracts. Together, these data suggest that caspase-3 is the primary inactivator of DFF45/ICAD and therefore the primary activator of apoptotic DNA fragmentation.

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Metadata

Authors
Wolf, B. B., Schuler, M., Echeverri, F., & Green, D. R.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1999-10
Volume
274
Issue
43
Pages
30651-30656
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2154554320
Cited by
487
References
2
FWCI
9.03
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Caspase-3 Is the Primary Activator of Apoptotic DNA Fragmentation via DNA Fragmentation Factor-45/Inhibitor of Caspase-activated DNase Inactivation. https://app.cochat.ai/papers/10.1074/jbc.274.43.30651
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Wolf, B. B., Schuler, M., Echeverri, F., & Green, D. R. (1999). Caspase-3 Is the Primary Activator of Apoptotic DNA Fragmentation via DNA Fragmentation Factor-45/Inhibitor of Caspase-activated DNase Inactivation. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.274.43.30651

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