GSBS Student Publications

Title

Sir2 mediates apoptosis through JNK-dependent pathways in Drosophila

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Biochemistry and Molecular Pharmacology

Date

6-20-2008

Document Type

Article

Medical Subject Headings

Animals; *Apoptosis; Cell Death; Cell Survival; Drosophila; Drosophila Proteins; Forkhead Transcription Factors; Histone Deacetylases; Immunohistochemistry; JNK Mitogen-Activated Protein Kinases; *MAP Kinase Signaling System; Phenotype; Sirtuins; Ultraviolet Rays

Disciplines

Life Sciences | Medicine and Health Sciences

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.

Rights and Permissions

Citation: Proc Natl Acad Sci U S A. 2008 Jun 24;105(25):8673-8. Epub 2008 Jun 17. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal Title

Proceedings of the National Academy of Sciences of the United States of America

PubMed ID

18562277