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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Yi, CH; Sogah, DK; Boyce, M; Degterev, A; Christofferson, DE; Yuan, J

Published Date

  • November 12, 2007

Published In

Volume / Issue

  • 179 / 4

Start / End Page

  • 619 - 626

PubMed ID

  • 17998402

Pubmed Central ID

  • 17998402

Electronic International Standard Serial Number (EISSN)

  • 1540-8140

International Standard Serial Number (ISSN)

  • 0021-9525

Digital Object Identifier (DOI)

  • 10.1083/jcb.200708090

Language

  • eng