Nature Genetics33, 522 - 526 (2003)
Published online: 17 March 2003; | doi:10.1038/ng1132
There is a Corrigendum (May 2003) associated with this Letter.
Sir3p phosphorylation by the Slt2p pathway effects redistribution of silencing function and shortened lifespan
Alo Ray1, 4, Ronald E. Hector1, 4, Nilanjan Roy1, 3, Jee-Hyeon Song1, Kathleen L. Berkner2
& Kurt W. Runge1
1
Department of Molecular Biology, NC20, Cleveland Clinic Foundation, Lerner Research Institute, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
2
Department of Molecular Cardiology, NB50, Cleveland Clinic Foundation, Lerner Research Institute, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
3
Present address: National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab 160062 India.
4
These authors contributed equally to this work.
Correspondence should be addressed to Kurt W. Runge rungek@ccf.org
An organism's lifespan is modulated by environmental conditions. When nutrients are abundant, the metabolism of many organisms shifts to growth or reproduction at the expense of longer lifespan, whereas a scarcity of nutrients reverses this shift1,
2,
3. These correlations suggest that organisms respond to environmental changes by altering their metabolism to promote either reproduction and growth or long life. The only previously reported signaling mechanism involved in this response is the nutrient-responsive insulin/insulin-like growth factor-1 receptor pathway1. Here we report another pathway that controls the length of yeast lifespan. Commitment to cell growth activates the Slt2p MAP kinase pathway, which phosphorylates the transcriptional silencing protein Sir3p, resulting in a shorter lifespan. Elimination of the Sir3p phosphorylation site at Ser275 extended lifespan by 38%. Lifespan extension occurs by a mechanism that is independent of suppressing rDNA recombination. Thus, Slt2p is an enzymatic regulator of silencing function that couples commitment to cell growth and shorter lifespan.
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