A genome-wide RNAi screen reveals multiple regulators of caspase activation.
Abstract
Apoptosis is an evolutionally conserved cellular suicide mechanism that can be activated
in response to a variety of stressful stimuli. Increasing evidence suggests that apoptotic
regulation relies on specialized cell death signaling pathways and also integrates
diverse signals from additional regulatory circuits, including those of cellular homeostasis.
We present a genome-wide RNA interference screen to systematically identify regulators
of apoptosis induced by DNA damage in Drosophila melanogaster cells. We identify 47
double- stranded RNA that target a functionally diverse set of genes, including several
with a known function in promoting cell death. Further characterization uncovers 10
genes that influence caspase activation upon the removal of Drosophila inhibitor of
apoptosis 1. This set includes the Drosophila initiator caspase Dronc and, surprisingly,
several metabolic regulators, a candidate tumor suppressor, Charlatan, and an N-acetyltransferase,
ARD1. Importantly, several of these genes show functional conservation in regulating
apoptosis in mammalian cells. Our data suggest a previously unappreciated fundamental
connection between various cellular processes and caspase-dependent cell death.
Type
Journal articleSubject
HemocytesCells, Cultured
Hela Cells
Embryo, Nonmammalian
Animals
Humans
Drosophila melanogaster
DNA Damage
Doxorubicin
Caspases
Acetyltransferases
Protein-Serine-Threonine Kinases
Drosophila Proteins
Transcription Factors
RNA, Small Interfering
Transfection
Cell Death
Apoptosis
Cell Survival
Epistasis, Genetic
Gene Silencing
RNA Interference
Enzyme Activation
Genome
bcl-2 Homologous Antagonist-Killer Protein
bcl-2-Associated X Protein
Inhibitor of Apoptosis Proteins
N-Terminal Acetyltransferase A
N-Terminal Acetyltransferase E
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https://hdl.handle.net/10161/19702Published Version (Please cite this version)
10.1083/jcb.200708090Publication Info
Yi, Caroline H; Sogah, Dodzie K; Boyce, Michael; Degterev, Alexei; Christofferson,
Dana E; & Yuan, Junying (2007). A genome-wide RNAi screen reveals multiple regulators of caspase activation. The Journal of cell biology, 179(4). pp. 619-626. 10.1083/jcb.200708090. Retrieved from https://hdl.handle.net/10161/19702.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Michael Scott Boyce
Associate Professor of Biochemistry
The Boyce Lab studies mammalian cell signaling through protein glycosylation. For
the latest news, project information and publications from our group, please visit
our web site at http://www.boycelab.org or follow us on Twitter at https://twitter.com/BoyceLab.

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