Sir3p phosphorylation by the Slt2p pathway effects redistribution of silencing function and shortened lifespan.
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 shift. 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 pathway. 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.
Ray
Alo
A
Department of Molecular Biology, NC20, Cleveland Clinic Foundation, Lerner Research Institute, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
Hector
Ronald E
RE
Roy
Nilanjan
N
Song
Jee-Hyeon
JH
Berkner
Kathleen L
KL
Runge
Kurt W
KW
D000483:Alleles; D015153:Blotting, Western; D005656:Fungal Proteins / Q000378:metabolism; D020868:Gene Silencing; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases; D008954:Models, Biological; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D016366:Open Reading Frames; D010641:Phenotype; D010766:Phosphorylation; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D011995:Recombination, Genetic; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors
D005656:Fungal Proteins; C084122:SIR3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D020928:Mitogen-Activated Protein Kinases; C072724:SLT2 protein, S cerevisiae