A genome-wide RNAi screen reveals multiple regulators of caspase activation.

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2007-11-12

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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.

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10.1083/jcb.200708090

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Yi, Caroline H, Dodzie K Sogah, Michael Boyce, Alexei Degterev, Dana E Christofferson and Junying Yuan (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.

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Boyce

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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