Sir2 mediates apoptosis through JNK-dependent pathways in Drosophila

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

Research output: Contribution to journalArticle

48 Citations (Scopus)

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

Fingerprint

MAP Kinase Signaling System
Drosophila
Yeasts
Apoptosis
Histone Deacetylases
Poisons
Caenorhabditis elegans
Caspases
Life Expectancy
Drosophila melanogaster
Diptera
Cell Survival
Cell Death
Diet

Keywords

  • Cell death
  • Deacetylase
  • dnaJ-H
  • Foxo

ASJC Scopus subject areas

  • General

Cite this

Sir2 mediates apoptosis through JNK-dependent pathways in Drosophila. / Griswold, Anthony; Chang, Karen T.; Runko, Alexander P.; Knight, Melanie A.; Min, Kyung Tai.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 25, 24.06.2008, p. 8673-8678.

Research output: Contribution to journalArticle

Griswold, Anthony ; Chang, Karen T. ; Runko, Alexander P. ; Knight, Melanie A. ; Min, Kyung Tai. / Sir2 mediates apoptosis through JNK-dependent pathways in Drosophila. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 25. pp. 8673-8678.
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