RRC ID 36223
Author Samejima K, Ogawa H, Ageichik AV, Peterson KL, Kaufmann SH, Kanemaki MT, Earnshaw WC.
Title Auxin-induced rapid degradation of inhibitor of caspase-activated DNase (ICAD) induces apoptotic DNA fragmentation, caspase activation, and cell death: a cell suicide module.
Journal J Biol Chem
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.
Volume 289(45)
Pages 31617-23
Published 2014-11-7
DOI 10.1074/jbc.M114.583542
PII S0021-9258(20)33384-6
PMID 25248749
PMC PMC4223357
MeSH Animals Annexin A5 / metabolism Apoptosis Apoptosis Regulatory Proteins / metabolism* Caspases / metabolism* Cell Death Cell Line, Tumor Cell Nucleus / metabolism Chickens DNA Fragmentation Deoxyribonucleases / metabolism* Enzyme Activation Fluorescent Antibody Technique, Indirect Gene Expression Regulation, Enzymologic* Gene Knockout Techniques Indoleacetic Acids / metabolism* Phosphatidylserines / metabolism Saccharomyces cerevisiae / enzymology
IF 4.238
Times Cited 18
Yeast BY25602