Auxin-induced rapid degradation of inhibitor of caspase-activated DNase (ICAD) induces apoptotic DNA fragmentation, caspase activation, and cell death: A cell suicide module

Kumiko Samejima, Hiromi Ogawa, Alexander V. Ageichik, Kevin L. Peterson, Scott H Kaufmann, Masato T. Kanemaki, William C. Earnshaw

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Caspase-activated DNase (CAD) is a major apoptotic nuclease, responsible for DNA fragmentation and chromatin condensation during apoptosis. CAD is normally activated in apoptosis as a result of caspase cleavage of its inhibitory chaperone ICAD. Other aspects of CAD regulation are poorly understood. In particular, it has been unclear whether direct CAD activation in non-apoptotic living cells can trigger cell death. Taking advantage of the auxin-inducible degron (AID) system, we have developed a suicide system with which ICAD is rapidly degraded in living cells in response to the plant hormone auxin. Our studies demonstrate that rapid ICAD depletion is sufficient to activate CAD and induce cell death in DT40 and yeast cells. In the vertebrate cells, ectopic CAD activation triggered caspase activation and subsequent hallmarks of caspase-dependent apoptotic changes, including phosphatidylserine exposure and nuclear fragmentation. These observations not only suggest that CAD activation drives apoptosis through a positive feedback loop, but also identify a unique suicide system that can be used for controlling gene-modified organisms.

Original languageEnglish (US)
Pages (from-to)31617-31623
Number of pages7
JournalJournal of Biological Chemistry
Volume289
Issue number45
DOIs
StatePublished - Nov 7 2014

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Indoleacetic Acids
DNA Fragmentation
Cell death
Caspases
Suicide
Cell Death
Chemical activation
Degradation
DNA
Cells
Apoptosis
Plant Growth Regulators
Deoxyribonucleases
Phosphatidylserines
caspase-activated deoxyribonuclease
caspase-activated DNase inhibitor
Yeast
Chromatin
Vertebrates
Condensation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Auxin-induced rapid degradation of inhibitor of caspase-activated DNase (ICAD) induces apoptotic DNA fragmentation, caspase activation, and cell death : A cell suicide module. / Samejima, Kumiko; Ogawa, Hiromi; Ageichik, Alexander V.; Peterson, Kevin L.; Kaufmann, Scott H; Kanemaki, Masato T.; Earnshaw, William C.

In: Journal of Biological Chemistry, Vol. 289, No. 45, 07.11.2014, p. 31617-31623.

Research output: Contribution to journalArticle

Samejima, Kumiko ; Ogawa, Hiromi ; Ageichik, Alexander V. ; Peterson, Kevin L. ; Kaufmann, Scott H ; Kanemaki, Masato T. ; Earnshaw, William C. / Auxin-induced rapid degradation of inhibitor of caspase-activated DNase (ICAD) induces apoptotic DNA fragmentation, caspase activation, and cell death : A cell suicide module. In: Journal of Biological Chemistry. 2014 ; Vol. 289, No. 45. pp. 31617-31623.
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