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Published online on August 8, 2007, 10.1073/pnas.0706121104
PNAS | August 14, 2007 | vol. 104 | no. 33 | 13355-13360


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BIOLOGICAL SCIENCES / CELL BIOLOGY
Expression of dominant-negative Dmp53 in the adult fly brain inhibits insulin signaling

Johannes H. Bauer, Chengyi Chang, Siti Nur Sarah Morris, Suzanne Hozier, Sandra Andersen, Joshua S. Waitzman, and Stephen L. Helfand*

Department of Molecular Biology, Cell Biology and Biochemistry, Division of Biology and Medicine, Brown University, Providence, RI 02903

Communicated by Anthony R. Cashmore, University of Pennsylvania, Philadelphia, PA, July 3, 2007 (received for review April 20, 2007)

In Drosophila melanogaster, p53 (Dmp53) is an important mediator of longevity. Expression of dominant-negative (DN) forms of Dmp53 in adult neurons, but not in muscle or fat body cells, extends lifespan. The lifespan of calorie-restricted flies is not further extended by simultaneously expressing DN-Dmp53 in the nervous system, indicating that a decrease in Dmp53 activity may be a part of the CR lifespan-extending pathway in flies. In this report, we show that selective expression of DN-Dmp53 in only the 14 insulin-producing cells (IPCs) in the brain extends lifespan to the same extent as expression in all neurons and this lifespan extension is not additive with CR. DN-Dmp53-dependent lifespan extension is accompanied by reduction of Drosophila insulin-like peptide 2 (dILP2) mRNA levels and reduced insulin signaling (IIS) in the fat body, which suggests that Dmp53 may affect lifespan by modulating insulin signaling in the fly.

Drosophila melanogaster | lifespan extension | p53

Author contributions: J.H.B. and S.L.H. designed research; J.H.B., C.C., S.N.S.M., S.H., S.A., and J.S.W. performed research; J.H.B. and C.C. contributed new reagents/analytic tools; J.H.B. and S.L.H. analyzed data; and J.H.B. and S.L.H. wrote the paper.

The authors declare no conflict of interest.

This article contains supporting information online at www.pnas.org/cgi/content/full/0706121104/DC1.

*To whom correspondence should be addressed. E-mail: stephen_helfand{at}brown.edu

© 2007 by The National Academy of Sciences of the USA


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