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A functional analysis reveals dependence on the anaphase-promoting complex for prolonged life span in yeast.
- Source :
-
Genetics [Genetics] 2004 Oct; Vol. 168 (2), pp. 759-74. - Publication Year :
- 2004
-
Abstract
- Defects in anaphase-promoting complex (APC) activity, which regulates mitotic progression and chromatin assembly, results in genomic instability, a hallmark of premature aging and cancer. We investigated whether APC-dependent genomic stability affects aging and life span in yeast. Utilizing replicative and chronological aging assays, the APC was shown to promote longevity. Multicopy expression of genes encoding Snf1p (MIG1) and PKA (PDE2) aging-pathway components suppressed apc5CA phenotypes, suggesting their involvement in APC-dependent longevity. While it is known that PKA inhibits APC activity and reduces life span, a link between the Snf1p-inhibited Mig1p transcriptional modulator and the APC is novel. Our mutant analysis supports a model in which Snf1p promotes extended life span by inhibiting the negative influence of Mig1p on the APC. Consistent with this, we found that increased MIG1 expression reduced replicative life span, whereas mig1Delta mutations suppressed the apc5CA chronological aging defect. Furthermore, Mig1p and Mig2p activate APC gene transcription, particularly on glycerol, and mig2Delta, but not mig1Delta, confers a prolonged replicative life span in both APC5 and acp5CA cells. However, glucose repression of APC genes was Mig1p and Mig2p independent, indicating the presence of an uncharacterized factor. Therefore, we propose that APC-dependent genomic stability is linked to prolonged longevity by the antagonistic regulation of the PKA and Snf1p pathways.
- Subjects :
- Anaphase-Promoting Complex-Cyclosome
Apc5 Subunit, Anaphase-Promoting Complex-Cyclosome
Cyclic Nucleotide Phosphodiesterases, Type 2
Phenotype
Phosphoric Diester Hydrolases genetics
Phosphoric Diester Hydrolases metabolism
Protein Serine-Threonine Kinases genetics
Protein Serine-Threonine Kinases metabolism
Saccharomyces cerevisiae genetics
Saccharomyces cerevisiae Proteins genetics
Transcription, Genetic
Ubiquitin-Protein Ligase Complexes antagonists & inhibitors
Ubiquitin-Protein Ligase Complexes genetics
Ubiquitin-Protein Ligases genetics
Aging physiology
Genomic Instability
Longevity
Saccharomyces cerevisiae metabolism
Saccharomyces cerevisiae Proteins metabolism
Ubiquitin-Protein Ligase Complexes metabolism
Ubiquitin-Protein Ligases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0016-6731
- Volume :
- 168
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Genetics
- Publication Type :
- Academic Journal
- Accession number :
- 15514051
- Full Text :
- https://doi.org/10.1534/genetics.104.027771