Divergent roles of RAS1 and RAS2 in yeast longevity

Individual cells of the yeast Saccharomyces cerevisiae have a limited replicative life-span. The role of the genes RAS1 and RAS2 in yeast longevity was examined. Overexpression of RAS2 led to a 30% increase in the life-span on average and postponed the senescence-related increase in generation time...

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Bibliographic Details
Published in:The Journal of biological chemistry 1994-07, Vol.269 (28), p.18638-18645
Main Authors: Sun, J, Kale, S.P, Childress, A.M, Pinswasdi, C, Jazwinski, S.M
Format: Article
Language:English
Subjects:
ADENOSINE MONOPHOSPHATE
ADENOSINMONOFOSFATO
Adenylyl Cyclases - biosynthesis
Ageing, cell death
ARN MENSAJERO
ARN MESSAGER
Biological and medical sciences
Blotting, Western
Cell physiology
Cloning, Molecular
Cyclic AMP - metabolism
EXPRESION GENICA
EXPRESSION DES GENES
Fundamental and applied biological sciences. Psychology
Fungal Proteins - biosynthesis
Fungal Proteins - genetics
Fungal Proteins - isolation & purification
GENE
Gene Deletion
Gene Expression
GENES
Genes, Fungal
Genes, ras
GTP-Binding Proteins - genetics
Kinetics
LONGEVIDAD
LONGEVITE
Molecular and cellular biology
MUTACION INDUCIDA
MUTATION PROVOQUEE
Plasmids
PROTEINAS
PROTEINE
ras Proteins
Restriction Mapping
SACCHAROMYCES CEREVISIAE
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - growth & development
Saccharomyces cerevisiae - physiology
Saccharomyces cerevisiae Proteins
Time Factors
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Summary:Individual cells of the yeast Saccharomyces cerevisiae have a limited replicative life-span. The role of the genes RAS1 and RAS2 in yeast longevity was examined. Overexpression of RAS2 led to a 30% increase in the life-span on average and postponed the senescence-related increase in generation time seen during yeast aging. No life-span extension was obtained by overexpression of RAS1. However, deletion of RAS1 prolonged the lifespan. These results suggest that RAS1 and RAS2 play reciprocal roles in determining yeast longevity. RAS1 and RAS2 mRNA and protein levels declined with replicative age, suggesting a diminishing impact on yeast longevity. The major known pathway through which Ras proteins function in yeast involves stimulation of adenylate cyclase. No evidence for a life-span-extending effect of elevated intracellular cAMP was found. Indeed, high intracellular cAMP was associated with curtailed lifespan. A similar decrease in life-span was found on disruption of BCY1, which codes for the regulatory subunit of protein kinase A, the downstream target of cAMP. Importantly, overexpression of an effector domain mutant of RAS2, defective in stimulation of adenylate cyclase, prolonged life-span to the same extent as the wildtype gene, suggesting that the cAMP pathway is neither sufficient nor necessary for increased longevity
ISSN:0021-9258
1083-351X
DOI:10.1016/S0021-9258(17)32357-8