CoChat
Sign Up
Cited by 275

The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.

MSN2 and MSN4 Link Calorie Restriction and TOR to Sirtuin-Mediated Lifespan Extension in Saccharomyces cerevisiae

Medvedik, Oliver, Lamming, Dudley W, Kim, Keyman D, Sinclair, David A·2007·PLoS Biology
DOI 10.1371/journal.pbio.0050261PMC PMC1994990
Open this paper in CoChat — free account

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.pbio.0050261

Cites

11 of 11 references verified0 citation errors · 0 not checkable

Statistics

Figures

Figure 1 MSN2/4 Are Required for Lifespan Extension by CR and Rapamycin (A) MSN2/4 are required for lifespan extension by CR (growth on 0.5% glucose). Average lifespans: W303 (wild-type [wt]) on 2% glucose, 25.0 divisions; W303 on CR diet, 30.8; msn2Δ/4Δ on 2% glucose, 24.2; and msn2Δ/4Δ on CR diet, 23.9. (B) The lifespans of msn2Δ and msn4Δ single mutants can be extended by CR. Average lifespans: msn2Δ on 2% glucose, 22.5 divisions; msn2Δ on CR diet, 29.9; msn4Δ on 2% glucose, 24.7; and msn4Δ on CR diet, 33.2. (C) MSN2/4 are required for lifespan extension by rapamycin (Rap). Average lifespans: wild-type, 23.3 divisions; wild-type + 1 nM rapamycin, 26.9; msn2Δ/4Δ, 23.8; and msn2Δ/4Δ + 1 nM rapamycin, 22.5.
Figure 1 MSN2/4 Are Required for Lifespan Extension by CR and Rapamycin (A) MSN2/4 are required for lifespan extension by CR (growth on 0.5% glucose). Average lifespans: W303 (wild-type [wt]) on 2% glucose, 25.0 divisions; W303 on CR diet, 30.8; msn2Δ/4Δ on 2% glucose, 24.2; and msn2Δ/4Δ on CR diet, 23.9. (B) The lifespans of msn2Δ and msn4Δ single mutants can be extended by CR. Average lifespans: msn2Δ on 2% glucose, 22.5 divisions; msn2Δ on CR diet, 29.9; msn4Δ on 2% glucose, 24.7; and msn4Δ on CR diet, 33.2. (C) MSN2/4 are required for lifespan extension by rapamycin (Rap). Average lifespans: wild-type, 23.3 divisions; wild-type + 1 nM rapamycin, 26.9; msn2Δ/4Δ, 23.8; and msn2Δ/4Δ + 1 nM rapamycin, 22.5.CC BY · PubMed Central
Figure 2 Effect of TOR Signaling on Sir2p Functions Requires MSN2/4 and PNC1 (A) Rapamycin and CR suppress rDNA recombination in an MSN2/4-dependent manner. (B) Deletion of PNC1 or treatment with NAM blocks the ability of CR or rapamycin treatment to lower rDNA recombination. (C) CR and rapamycin treatment do not increase Sir2p levels. (D) Deletion of PNC1 blocks the ability of rapamycin to extend lifespan. Average lifespans: wild-type (wt), 23.3 divisions; wild-type + 1 nM rapamycin, 26.9; pnc1Δ, 20.9; and pnc1Δ + 1 nM rapamycin, 21.4. (E) Overexpression (o/e) of PNC1 suppresses rDNA recombination in both wild-type and msn2Δ/4Δ strains. (F) Expression of PNC1 can extend the lifespan of a strain lacking MSN2/4. Average lifespans: wild-type, 23.2 divisions; wild-type + PNC1, 28.0; msn2Δ/4Δ, 22.0; and msn2Δ/4Δ + PNC1, 27.3. Glu, glucose; Rap, rapamycin.
Figure 2 Effect of TOR Signaling on Sir2p Functions Requires MSN2/4 and PNC1 (A) Rapamycin and CR suppress rDNA recombination in an MSN2/4-dependent manner. (B) Deletion of PNC1 or treatment with NAM blocks the ability of CR or rapamycin treatment to lower rDNA recombination. (C) CR and rapamycin treatment do not increase Sir2p levels. (D) Deletion of PNC1 blocks the ability of rapamycin to extend lifespan. Average lifespans: wild-type (wt), 23.3 divisions; wild-type + 1 nM rapamycin, 26.9; pnc1Δ, 20.9; and pnc1Δ + 1 nM rapamycin, 21.4. (E) Overexpression (o/e) of PNC1 suppresses rDNA recombination in both wild-type and msn2Δ/4Δ strains. (F) Expression of PNC1 can extend the lifespan of a strain lacking MSN2/4. Average lifespans: wild-type, 23.2 divisions; wild-type + PNC1, 28.0; msn2Δ/4Δ, 22.0; and msn2Δ/4Δ + PNC1, 27.3. Glu, glucose; Rap, rapamycin.CC BY · PubMed Central
Figure 3 MSN2/4 Regulate the Expression of PNC1 (A) Expression of Pnc1p-GFP is induced by CR and by rapamycin. (B) Western blotting shows that CR and rapamycin induce high levels of Pnc1p in an MSN2/4-dependent manner. (C) A cdc25–10 mutant has increased expression of PNC1 but not if MSN2/4 are deleted. (D) Increased expression of PNC1 in response to salt stress, osmotic stress, and amino acid restriction requires MSN2/4, but increased expression of PNC1 in response to heat shock does not. (E) MSN2/4 are not required for lifespan extension by heat shock. Average lifespans: wild-type at 30 °C, 22.2 divisions; wild-type at 37 °C, 26.8; msn2Δ/4Δ at 30 °C, 20.7; and msn2Δ/4Δ at 37 °C, 25.8. (F) Heat shock induction of PNC1 in an msn2Δ/4Δ strain is dependent upon HSF1. 2/4Δ, msn2Δ/4Δ; dox, doxycycline; Glu, glucose; low a.a., low amino acids; rap, rapamycin; Sorb, sorbitol; wt, wild-type.
Figure 3 MSN2/4 Regulate the Expression of PNC1 (A) Expression of Pnc1p-GFP is induced by CR and by rapamycin. (B) Western blotting shows that CR and rapamycin induce high levels of Pnc1p in an MSN2/4-dependent manner. (C) A cdc25–10 mutant has increased expression of PNC1 but not if MSN2/4 are deleted. (D) Increased expression of PNC1 in response to salt stress, osmotic stress, and amino acid restriction requires MSN2/4, but increased expression of PNC1 in response to heat shock does not. (E) MSN2/4 are not required for lifespan extension by heat shock. Average lifespans: wild-type at 30 °C, 22.2 divisions; wild-type at 37 °C, 26.8; msn2Δ/4Δ at 30 °C, 20.7; and msn2Δ/4Δ at 37 °C, 25.8. (F) Heat shock induction of PNC1 in an msn2Δ/4Δ strain is dependent upon HSF1. 2/4Δ, msn2Δ/4Δ; dox, doxycycline; Glu, glucose; low a.a., low amino acids; rap, rapamycin; Sorb, sorbitol; wt, wild-type.CC BY · PubMed Central
Figure 4 Msn2p Localizes to the Nucleus during CR (A) CR promotes increased nuclear migration of Msn2p-GFP in a dose-dependent manner. (B) Quantification of the percent of cells with predominately nuclear Msn2p-GFP or Msn4p-GFP. (C) Deletion of TOR1 promotes nuclear localization of Msn2p-GFP. (D) A cdc25–10 mutant has increased nuclear localization of Msn2p-GFP.
Figure 4 Msn2p Localizes to the Nucleus during CR (A) CR promotes increased nuclear migration of Msn2p-GFP in a dose-dependent manner. (B) Quantification of the percent of cells with predominately nuclear Msn2p-GFP or Msn4p-GFP. (C) Deletion of TOR1 promotes nuclear localization of Msn2p-GFP. (D) A cdc25–10 mutant has increased nuclear localization of Msn2p-GFP.CC BY · PubMed Central
Figure 5 CR Induces Nucleo-Cytoplasmic Oscillations of Msn2p-GFP During CR, Msn2p-GFP oscillates between the cytoplasm and nucleus. (A and B) Cells grown at 2% glucose concentrations (A) exhibit exclusively cytoplasmic localization of Msn2p-GFP. Cells placed in medium containing 0% glucose (B) exhibit exclusively nuclear localization of Msn2p-GFP. For cells in 2% glucose or 0% glucose, a plot of the ratio of average nuclear intensity versus average cytoplasmic intensity for a single representative cell, labeled with an arrowhead in the respective photomicrographs, is shown. (C) During CR conditions, cells exhibit nucleo-cytoplasmic oscillations of Msn2p-GFP with a periodicity of ∼2–3 min. A representative population of cells is shown at 0.1% glucose concentrations. The ratios of average nuclear intensity versus average cytoplasmic intensity for three representative cells, labeled a, b, and c, are shown plotted over the course of 20 min beneath the photomicrographs.
Figure 5 CR Induces Nucleo-Cytoplasmic Oscillations of Msn2p-GFP During CR, Msn2p-GFP oscillates between the cytoplasm and nucleus. (A and B) Cells grown at 2% glucose concentrations (A) exhibit exclusively cytoplasmic localization of Msn2p-GFP. Cells placed in medium containing 0% glucose (B) exhibit exclusively nuclear localization of Msn2p-GFP. For cells in 2% glucose or 0% glucose, a plot of the ratio of average nuclear intensity versus average cytoplasmic intensity for a single representative cell, labeled with an arrowhead in the respective photomicrographs, is shown. (C) During CR conditions, cells exhibit nucleo-cytoplasmic oscillations of Msn2p-GFP with a periodicity of ∼2–3 min. A representative population of cells is shown at 0.1% glucose concentrations. The ratios of average nuclear intensity versus average cytoplasmic intensity for three representative cells, labeled a, b, and c, are shown plotted over the course of 20 min beneath the photomicrographs.CC BY · PubMed Central
Figure 6 Deletion of MSN2/4 Abrogates Expression of LacZ Reporter Constructs Driven by the PNC1 Promoter (A) Reporter constructs for analysis of STRE and Msn2p/4p function. (B) β-galactosidase activity of reporter constructs in wild-type (wt) cells grown in 2% YPD (Glu) (white bars), 0.5% YPD (black bars), or 2%YPD at 37 °C (grey bars). (C–E) Activity of reporter constructs in (C) an msn2Δ/4Δ strain, (D) an msn2Δ strain, or (E) an msn4Δ strain. Activity is listed as nanomoles of cleaved o-nitrophenol-β-D-galactopyranoside substrate per minute per milligram total protein.
Figure 6 Deletion of MSN2/4 Abrogates Expression of LacZ Reporter Constructs Driven by the PNC1 Promoter (A) Reporter constructs for analysis of STRE and Msn2p/4p function. (B) β-galactosidase activity of reporter constructs in wild-type (wt) cells grown in 2% YPD (Glu) (white bars), 0.5% YPD (black bars), or 2%YPD at 37 °C (grey bars). (C–E) Activity of reporter constructs in (C) an msn2Δ/4Δ strain, (D) an msn2Δ strain, or (E) an msn4Δ strain. Activity is listed as nanomoles of cleaved o-nitrophenol-β-D-galactopyranoside substrate per minute per milligram total protein.CC BY · PubMed Central
Figure 7 Msn2p Directly Regulates PNC1 (A) Nuclear localization of Msn2p is sufficient to induce PNC1. (B) Chromatin immunoprecipitation analysis of Msn2p-HA binding to the PNC1 promoter. IN, input; IP, immunoprecipitation. (C) Relative enrichment of Msn2p-HA at the PNC1 promoter shows increased promoter binding during CR.
Figure 7 Msn2p Directly Regulates PNC1 (A) Nuclear localization of Msn2p is sufficient to induce PNC1. (B) Chromatin immunoprecipitation analysis of Msn2p-HA binding to the PNC1 promoter. IN, input; IP, immunoprecipitation. (C) Relative enrichment of Msn2p-HA at the PNC1 promoter shows increased promoter binding during CR.CC BY · PubMed Central
Figure 8 Model of How TOR Signaling and CR Regulate Yeast Replicative Lifespan CR and TOR signaling regulate the nuclear localization of Msn2p/4p. When localized to the nucleus, Msn2p/4p promote the transcription of PNC1, a nicotinamidase. The removal of NAM by Pnc1p increases the activity of sirtuins, including Sir2p and Hst2p, which promote longevity by stabilizing the yeast rDNA array and preventing the formation of ERCs. TOR signaling may also regulate lifespan by sirtuin-independent pathways, such as the regulation of ribosomal biogenesis.
Figure 8 Model of How TOR Signaling and CR Regulate Yeast Replicative Lifespan CR and TOR signaling regulate the nuclear localization of Msn2p/4p. When localized to the nucleus, Msn2p/4p promote the transcription of PNC1, a nicotinamidase. The removal of NAM by Pnc1p increases the activity of sirtuins, including Sir2p and Hst2p, which promote longevity by stabilizing the yeast rDNA array and preventing the formation of ERCs. TOR signaling may also regulate lifespan by sirtuin-independent pathways, such as the regulation of ribosomal biogenesis.CC BY · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 11 references

Research works printed but not linked: 69

  1. Jiang, 2000, FASEB J, 14, 2135
  2. Barton, 1950, J Gen Microbiol, 4, 84
  3. Sinclair, 1998, Trends Biochem Sci, 23, 131
  4. Sinclair, 1997, Cell, 91, 1033
  5. Guarente, 2000, Genes Dev, 14, 1021
  6. Kaeberlein, 1999, Genes Dev, 13, 2570
  7. Fritze, 1997, EMBO J, 16, 6495
  8. Howitz, 2003, Nature, 425, 191
  9. Tissenbaum, 2001, Nature, 410, 227
  10. Wood, 2004, Nature, 430, 686
  11. Viswanathan, 2005, Dev Cell, 9, 605
  12. Rogina, 2004, Proc Natl Acad Sci U S A, 101, 15998
  13. McCay, 1975, Nutr Rev, 33, 241
  14. Lin, 2000, Science, 289, 2126
  15. Lamming, 2005, Science, 309, 1861
  16. Wang, 2006, Mech Ageing Dev, 127, 48
  17. Kaeberlein, 2005, Science, 310, 1193
  18. Kaeberlein, 2004, PLoS Biol, 2, e296
  19. Wullschleger, 2006, Cell, 124, 471
  20. Vellai, 2003, Nature, 426, 620
  21. Kapahi, 2004, Curr Biol, 14, 885
  22. Syntichaki, 2007, Nature, 445, 922
  23. Hansen, 2007, Aging Cell, 6, 95
  24. Bitterman, 2002, J Biol Chem, 277, 45099
  25. Sauve, 2005, Mol Cell, 17, 595
  26. Jackson, 2003, J Biol Chem, 278, 50985
  27. Gallo, 2004, Mol Cell Biol, 24, 1301
  28. Anderson, 2003, Nature, 423, 181
  29. Anderson, 2002, J Biol Chem, 277, 18881
  30. van der Veer, 2007, J Biol Chem, 282, 10841
  31. Revollo, 2004, J Biol Chem, 279, 50754
  32. Ghislain, 2002, Yeast, 19, 215
  33. Fabrizio, 2001, Science, 292, 288
  34. Fabrizio, 2003, Genetics, 163, 35
  35. Aparicio, 1991, Cell, 66, 1279
  36. Gorner, 1998, Genes Dev, 12, 586
  37. Lin, 2002, Nature, 418, 344
  38. Ferguson, 2005, Genetics, 169, 1203
  39. Gorner, 2002, EMBO J, 21, 135
  40. Powers, 2006, Genes Dev, 20, 174
  41. Beck, 1999, Nature, 402, 689
  42. Jacquet, 2003, J Cell Biol, 161, 497
  43. Enninga, 2003, Mol Cell Biol, 23, 7271
  44. Smith, 1998, EMBO J, 17, 3556
  45. DeRisi, 1997, Science, 278, 680
  46. Gasch, 2000, Mol Biol Cell, 11, 4241
  47. Moskvina, 1998, Yeast, 14, 1041
  48. Orlova, 2006, Eukaryot Cell, 5, 1831
  49. Ashrafi, 2000, Genes Dev, 14, 1872
  50. Young, 2002, J Biol Chem, 277, 38095
  51. Seker, 2003, Folia Microbiol (Praha), 48, 193
  52. Deminoff, 2001, Genetics, 158, 133
  53. Easlon, 2007, J Biol Chem, 282, 6161
  54. Tsang, 2007, EMBO J, 26, 448
  55. Morrow, 2004, J Biol Chem, 279, 43382
  56. Selsby, 2005, Exp Gerontol, 40, 37
  57. Longo, 2003, Exp Gerontol, 38, 807
  58. Fabrizio, 2004, FEBS Lett, 557, 136
  59. Fabrizio, 2005, Cell, 123, 655
  60. Masoro, 2000, Hum Exp Toxicol, 19, 340
  61. Sinclair, 2005, Mech Ageing Dev, 126, 987
  62. Bitterman, 2003, Microbiol Mol Biol Rev, 67, 376
  63. Mostoslavsky, 2006, Cell, 124, 315
  64. Lamming, 2006, Science, 312, 1312
  65. Longtine, 1998, Yeast, 14, 953
  66. Goldstein, 1999, Yeast, 15, 1541
  67. Heitman, 1991, Science, 253, 905
  68. Strahl-Bolsinger, 1997, Genes Dev, 11, 83
  69. Huang, 2003, Genes Dev, 17, 2162

Cited by

Sorted by citations

Metadata

Authors
Medvedik, O., Lamming, D. W., Kim, K. D., & Sinclair, D. A.
Venue
PLoS Biology
Publisher
Public Library of Science (PLoS)
Published
2007-10-02
Volume
5
Issue
10
Pages
e261
ISSN
1545-7885
DOI
10.1371/journal.pbio.0050261
PMC
PMC1994990
Cited by
275
References
11
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (unspecified)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review