Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Genes & Dev. 14 (15): 1872-1885

Copyright © 2000 by Cold Spring Harbor Laboratory Press.

Vol. 14, No. 15, pp. 1872-1885, August 1, 2000

Sip2p and its partner Snf1p kinase affect aging in S. cerevisiae

Kaveh Ashrafi, Stephen S. Lin, Jill K. Manchester, and Jeffrey I. Gordon1

Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110 USA

For a number of organisms, the ability to withstand periods of nutrient deprivation correlates directly with lifespan. However, the underlying molecular mechanisms are poorly understood. We show that deletion of the N-myristoylprotein, Sip2p, reduces resistance to nutrient deprivation and shortens lifespan in Saccharomyces cerevisiae. This reduced lifespan is due to accelerated aging, as defined by loss of silencing from telomeres and mating loci, nucleolar fragmentation, and accumulation of extrachromosomal rDNA. Genetic studies indicate that sip2Delta produces its effect on aging by increasing the activity of Snf1p, a serine/threonine kinase involved in regulating global cellular responses to glucose starvation. Biochemical analyses reveal that as yeast age, hexokinase activity increases as does cellular ATP and NAD+ content. The change in glucose metabolism represents a new correlate of aging in yeast and occurs to a greater degree, and at earlier generational ages in sip2Delta cells. Sip2p and Snf1p provide new molecular links between the regulation of cellular energy utilization and aging.

[Key Words: Aging; Saccharomyces cervisiae; N-myristoylproteins; Snf1p kinase interacting protein-2; glucose metabolism; cellular energy storage]

1 Corresponding author.

GENES & DEVELOPMENT 14:1872-1885 © 2000 by Cold Spring Harbor Laboratory Press  ISSN 0890-9369/00 $5.00

Activation of Protein Kinase C-Mitogen-activated Protein Kinase Signaling in Response to Inositol Starvation Triggers Sir2p-dependent Telomeric Silencing in Yeast.
S. Lee, M. L. Gaspar, M. A. Aregullin, S. A. Jesch, and S. A. Henry (2013)
J. Biol. Chem. 288, 27861-27871
   Abstract »    Full Text »    PDF »
Nutritional Control of Growth and Development in Yeast.
J. R. Broach (2012)
Genetics 192, 73-105
   Abstract »    Full Text »    PDF »
Calorie Restriction: Is AMPK a Key Sensor and Effector?.
C. Canto and J. Auwerx (2011)
Physiology 26, 214-224
   Abstract »    Full Text »    PDF »
A network biology approach to aging in yeast.
D. R. Lorenz, C. R. Cantor, and J. J. Collins (2009)
PNAS 106, 1145-1150
   Abstract »    Full Text »    PDF »
Cyclic AMP-Protein Kinase A and Snf1 Signaling Mechanisms Underlie the Superior Potency of Sucrose for Induction of Filamentation in Saccharomyces cerevisiae.
S. Van de Velde and J. M. Thevelein (2008)
Eukaryot. Cell 7, 286-293
   Abstract »    Full Text »    PDF »
Chronological and replicative life-span extension in Saccharomyces cerevisiae by increased dosage of alcohol dehydrogenase 1.
G. Reverter-Branchat, E. Cabiscol, J. Tamarit, M. A. Sorolla, M. Angeles de la Torre, and J. Ros (2007)
Microbiology 153, 3667-3676
   Abstract »    Full Text »    PDF »
N-Myristoylation Regulates the SnRK1 Pathway in Arabidopsis.
M. Pierre, J. A. Traverso, B. Boisson, S. Domenichini, D. Bouchez, C. Giglione, and T. Meinnel (2007)
PLANT CELL 19, 2804-2821
   Abstract »    Full Text »    PDF »
Thioredoxin-Linked Proteins Are Reduced during Germination of Medicago truncatula Seeds.
F. Alkhalfioui, M. Renard, W. H. Vensel, J. Wong, C. K. Tanaka, W. J. Hurkman, B. B. Buchanan, and F. Montrichard (2007)
Plant Physiology 144, 1559-1579
   Abstract »    Full Text »    PDF »
Regulation of Snf1 Protein Kinase in Response to Environmental Stress.
S.-P. Hong and M. Carlson (2007)
J. Biol. Chem. 282, 16838-16845
   Abstract »    Full Text »    PDF »
Nitrogen Availability and TOR Regulate the Snf1 Protein Kinase in Saccharomyces cerevisiae.
M. Orlova, E. Kanter, D. Krakovich, and S. Kuchin (2006)
Eukaryot. Cell 5, 1831-1837
   Abstract »    Full Text »    PDF »
Yeast AMID Homologue Ndi1p Displays Respiration-restricted Apoptotic Activity and Is Involved in Chronological Aging.
W. Li, L. Sun, Q. Liang, J. Wang, W. Mo, and B. Zhou (2006)
Mol. Biol. Cell 17, 1802-1811
   Abstract »    Full Text »    PDF »
Glucose Signaling in Saccharomyces cerevisiae.
G. M. Santangelo (2006)
Microbiol. Mol. Biol. Rev. 70, 253-282
   Abstract »    Full Text »    PDF »
Carbon Source-dependent Assembly of the Snf1p Kinase Complex in Candida albicans.
C. Corvey, P. Koetter, T. Beckhaus, J. Hack, S. Hofmann, M. Hampel, T. Stein, M. Karas, and K.-D. Entian (2005)
J. Biol. Chem. 280, 25323-25330
   Abstract »    Full Text »    PDF »
Role of Tos3, a Snf1 Protein Kinase Kinase, during Growth of Saccharomyces cerevisiae on Nonfermentable Carbon Sources.
M.-D. Kim, S.-P. Hong, and M. Carlson (2005)
Eukaryot. Cell 4, 861-866
   Abstract »    Full Text »    PDF »
Contribution of CAF-I to Anaphase-Promoting-Complex-Mediated Mitotic Chromatin Assembly in Saccharomyces cerevisiae.
T. A. A. Harkness, T. G. Arnason, C. Legrand, M. G. Pisclevich, G. F. Davies, and E. L. Turner (2005)
Eukaryot. Cell 4, 673-684
   Abstract »    Full Text »    PDF »
Aging Elevates Basal Adenosine Monophosphate-Activated Protein Kinase (AMPK) Activity and Eliminates Hypoxic Activation of AMPK in Mouse Liver.
J. D. Mulligan, A. A. Gonzalez, R. Kumar, A. J. Davis, and K. W. Saupe (2005)
J Gerontol A Biol Sci Med Sci 60, 21-27
   Abstract »    Full Text »    PDF »
A Functional Analysis Reveals Dependence on the Anaphase-Promoting Complex for Prolonged Life Span in Yeast.
T. A. A. Harkness, K. A. Shea, C. Legrand, M. Brahmania, and G. F. Davies (2004)
Genetics 168, 759-774
   Abstract »    Full Text »    PDF »
Pak1 Protein Kinase Regulates Activation and Nuclear Localization of Snf1-Gal83 Protein Kinase.
K. Hedbacker, S.-P. Hong, and M. Carlson (2004)
Mol. Cell. Biol. 24, 8255-8263
   Abstract »    Full Text »    PDF »
Snf1-related protein kinase 1 is needed for growth in a normal day-night light cycle.
M. Thelander, T. Olsson, and H. Ronne (2004)
EMBO J. 23, 1900-1910
   Abstract »    Full Text »    PDF »
The Glucose-regulated Nuclear Localization of Hexokinase 2 in Saccharomyces cerevisiae Is Mig1-dependent.
D. Ahuatzi, P. Herrero, T. de la Cera, and F. Moreno (2004)
J. Biol. Chem. 279, 14440-14446
   Abstract »    Full Text »    PDF »
The Protein Kinase Snf1 Is Required for Tolerance to the Ribonucleotide Reductase Inhibitor Hydroxyurea.
C. Dubacq, A. Chevalier, and C. Mann (2004)
Mol. Cell. Biol. 24, 2560-2572
   Abstract »    Full Text »    PDF »
Cyclic AMP-Dependent Protein Kinase Regulates the Subcellular Localization of Snf1-Sip1 Protein Kinase.
K. Hedbacker, R. Townley, and M. Carlson (2004)
Mol. Cell. Biol. 24, 1836-1843
   Abstract »    Full Text »    PDF »
Calorie restriction extends yeast life span by lowering the level of NADH.
S.-J. Lin, E. Ford, M. Haigis, G. Liszt, and L. Guarente (2004)
Genes & Dev. 18, 12-16
   Abstract »    Full Text »    PDF »
Insulin/IGF-I-signaling pathway: an evolutionarily conserved mechanism of longevity from yeast to humans.
M. Barbieri, M. Bonafe, C. Franceschi, and G. Paolisso (2003)
Am J Physiol Endocrinol Metab 285, E1064-E1071
   Abstract »    Full Text »    PDF »
Longevity Regulation in Saccharomyces cerevisiae: Linking Metabolism, Genome Stability, and Heterochromatin.
K. J. Bitterman, O. Medvedik, and D. A. Sinclair (2003)
Microbiol. Mol. Biol. Rev. 67, 376-399
   Abstract »    Full Text »    PDF »
Activation of yeast Snf1 and mammalian AMP-activated protein kinase by upstream kinases.
S.-P. Hong, F. C. Leiper, A. Woods, D. Carling, and M. Carlson (2003)
PNAS 100, 8839-8843
   Abstract »    Full Text »    PDF »
Is DNA Cut Out for a Long Life?.
D. Sinclair (2003)
Sci. Aging Knowl. Environ. 2003, pe8-8
   Abstract »    Full Text »
Sip2, an N-Myristoylated beta Subunit of Snf1 Kinase, Regulates Aging in Saccharomyces cerevisiae by Affecting Cellular Histone Kinase Activity, Recombination at rDNA Loci, and Silencing.
S. S. Lin, J. K. Manchester, and J. I. Gordon (2003)
J. Biol. Chem. 278, 13390-13397
   Abstract »    Full Text »    PDF »
Snf1 Kinases with Different {beta}-Subunit Isoforms Play Distinct Roles in Regulating Haploid Invasive Growth.
V. K. Vyas, S. Kuchin, C. D. Berkey, and M. Carlson (2003)
Mol. Cell. Biol. 23, 1341-1348
   Abstract »    Full Text »    PDF »
Yap1 Accumulates in the Nucleus in Response to Carbon Stress in Saccharomyces cerevisiae.
H. A. Wiatrowski and M. Carlson (2003)
Eukaryot. Cell 2, 19-26
   Abstract »    Full Text »    PDF »
Std1p (Msn3p) Positively Regulates the Snf1 Kinase in Saccharomyces cerevisiae.
S. Kuchin, V. K. Vyas, E. Kanter, S.-P. Hong, and M. Carlson (2003)
Genetics 163, 507-514
   Abstract »    Full Text »    PDF »
Modification of Brain Aging and Neurodegenerative Disorders by Genes, Diet, and Behavior.
M. P. Mattson, S. L. Chan, and W. Duan (2002)
Physiol Rev 82, 637-672
   Abstract »    Full Text »    PDF »
Manipulation of a Nuclear NAD+ Salvage Pathway Delays Aging without Altering Steady-state NAD+ Levels.
R. M. Anderson, K. J. Bitterman, J. G. Wood, O. Medvedik, H. Cohen, S. S. Lin, J. K. Manchester, J. I. Gordon, and D. A. Sinclair (2002)
J. Biol. Chem. 277, 18881-18890
   Abstract »    Full Text »    PDF »
Sugar Sensing and Signaling in Plants.
F. Rolland, B. Moore, and J. Sheen (2002)
PLANT CELL 14, S185-S205
   Full Text »    PDF »
Telomeric and rDNA Silencing in Saccharomyces cerevisiae Are Dependent on a Nuclear NAD+ Salvage Pathway.
J. J. Sandmeier, I. Celic, J. D. Boeke, and J. S. Smith (2002)
Genetics 160, 877-889
   Abstract »    Full Text »    PDF »
Interaction of the Repressors Nrg1 and Nrg2 With the Snf1 Protein Kinase in Saccharomyces cerevisiae.
V. K. Vyas, S. Kuchin, and M. Carlson (2001)
Genetics 158, 563-572
   Abstract »    Full Text »    PDF »
Subcellular localization of the Snf1 kinase is regulated by specific {beta} subunits and a novel glucose signaling mechanism.
O. Vincent, R. Townley, S. Kuchin, and M. Carlson (2001)
Genes & Dev. 15, 1104-1114
   Abstract »    Full Text »
Enhanced Gluconeogenesis and Increased Energy Storage as Hallmarks of Aging in Saccharomyces cerevisiae.
S. S. Lin, J. K. Manchester, and J. I. Gordon (2001)
J. Biol. Chem. 276, 36000-36007
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882