Sir2 mediates apoptosis through JNK-dependent pathways in Drosophila

Anthony J. Griswold, Karen T. Chang, Alexander P. Runko, Melanie A. Knight, Kyung Tai Min

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Increased expression of the histone deacetylase sir2 has been reported to extend the life span of diverse organisms including yeast, Caenorhabditis elegans, and Drosophila melanogaster. A small molecule activator of Sir2, resveratrol, has also been suggested to extend the fitness and survival of these simple model organisms as well as mice fed high calorie diets. However, other studies in yeast have shown that Sir2 itself may prevent life extension, and high expression levels of Sir2 can be toxic to yeast and mouse cells. This conflicting evidence highlights the importance of understanding the mechanisms by which Sir2 expression or activation affects survival of organisms. To investigate the downstream signaling pathways affected by Sir2 in Drosophila, we generated transgenic flies expressing sir2. Here, we show that overexpression of sir2 in Drosophila promotes caspase-dependent but p53-independent apoptosis that is mediated by the JNK and FOXO signaling pathways. Furthermore, we find that a loss-of-function sir2 mutant partially prevents apoptosis induced by UV irradiation in the eye. Together, these results suggest that Sir2 normally participates in the regulation of cell survival and death in Drosophila.

Original languageEnglish (US)
Pages (from-to)8673-8678
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number25
DOIs
StatePublished - Jun 24 2008
Externally publishedYes

Keywords

  • Cell death
  • Deacetylase
  • Foxo
  • dnaJ-H

ASJC Scopus subject areas

  • General

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