The DOI matches its Crossref record; 63 of the 64 references it cites were found in a registry or an index.
SIRT1 Acts as a Nutrient-sensitive Growth Suppressor and Its Loss Is Associated with Increased AMPK and Telomerase Activity
Open accessAbstract
SIRT1, the mammalian homolog of SIR2 in Saccharomyces cerevisiae, is an NAD-dependent deacetylase implicated in regulation of lifespan. By designing effective short hairpin RNAs and a silent shRNA-resistant mutant SIRT1 in a genetically defined system, we show that efficient inhibition of SIRT1 in telomerase-immortalized human cells enhanced cell growth under normal and nutrient limiting conditions. Hematopoietic stem cells obtained from SIRT1-deficient mice also showed increased growth capacity and decreased dependency on growth factors. Consistent with this, SIRT1 inhibition was associated with increased telomerase activity in human cells. We also observed a significant increase in AMPK levels up on SIRT1 inhibition under glucose limiting conditions. Although SIRT1 suppression cooperated with hTERT to promote cell growth, either overexpression or suppression of SIRT1 alone had no effect on life span of human diploid fibroblasts. Our findings challenge certain models and connect nutrient sensing enzymes to the immortalization process. Furthermore, they show that in certain cell lineages, SIRT1 can act as a growth suppressor gene.
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“Signaling pathways related to nutrient sensing and uptake, such as SIRT1, AMPK and FoxO, may represent molecular effectors of the benefits of CR on stem cell activity113,114, although a complete understanding of how CR affects stem cell function must await further studies.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [113]
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Cites
The serial cultivation of human diploid cell strains
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Specific Association of Human Telomerase Activity with Immortal Cells and Cancer
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“Consistent with this model telomerase is reactivated in immortal human cells (Counter et al., 1992; Kim et al., 1994).”
BackgroundTelomeres shorten during ageing of human fibroblasts
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Extension of Life-Span by Introduction of Telomerase into Normal Human Cells
Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C.-P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., & Wright, W. E. (1998) · Science · doi:10.1126/science.279.5349.349 · Cited by 4,975
Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
Imai, S.-I., Armstrong, C. M., Kaeberlein, M., & Guarente, L. (2000) · Nature · doi:10.1038/35001622 · Cited by 3,510
Identification of a specific telomere terminal transferase activity in tetrahymena extracts
Greider, C. W., & Blackburn, E. H. (1985) · Cell · doi:10.1016/0092-8674(85)90170-9 · Cited by 3,400
Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase
Brunet, A., Sweeney, L. B., Sturgill, J. F., Chua, K. F., Greer, P. L., Lin, Y., Tran, H., Ross, S. E., Mostoslavsky, R., Cohen, H. Y., et al. (2004) · Science · doi:10.1126/science.1094637 · Cited by 3,239
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Modulation of NF‐κB‐dependent transcription and cell survival by the SIRT1 deacetylase
Yeung, F., Hoberg, J. E., Ramsey, C. S., Keller, M. D., Jones, D. R., Frye, R. A., & Mayo, M. W. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600244 · Cited by 2,750
hSIR2SIRT1 Functions as an NAD-Dependent p53 Deacetylase
Vaziri, H., Dessain, S. K., Eaton, E. N., Imai, S., Frye, R. A., Pandita, T. K., Guarente, L., & Weinberg, R. A. (2001) · Cell · doi:10.1016/s0092-8674(01)00527-x · Cited by 2,690
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Mammalian Sirtuins: Biological Insights and Disease Relevance
Haigis, M. C., & Sinclair, D. A. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathol.4.110807.092250 · Cited by 2,085
Stem cell aging: mechanisms, regulators and therapeutic opportunities
Oh, J., Lee, Y. D., & Wagers, A. J. (2014) · Nature Medicine · doi:10.1038/nm.3651 · Cited by 796
AMP-activated protein kinase-deficient mice are resistant to the metabolic effects of resveratrol
Um, J.-H., Park, S.-J., Kang, H., Yang, S., Foretz, M., McBurney, M. W., Kim, M. K., Viollet, B., & Chung, J. H. (2010) · Diabetes · doi:10.2337/db09-0482 · Cited by 647
The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth.
Firestein, R., Blander, G., Michan, S., Oberdoerffer, P., Ogino, S., Campbell, J., Bhimavarapu, A., Luikenhuis, S., de Cabo, R., Fuchs, C., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002020 · Cited by 588
The molecular targets of resveratrol
Kulkarni, S. S., & Cantó, C. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.10.005 · Cited by 477
Metadata
- Authors
- Narala, S. R., Allsopp, R. C., Wells, T. B., Zhang, G., Prasad, P., Coussens, M. J., Rossi, D. J., Weissman, I. L., & Vaziri, H.
- Affiliations
- University of Toronto (CA)
- University of Hawaiʻi at Mānoa (US)
- Institute for Stem Cell Biology and Regenerative Medicine (US)
- Venue
- Molecular Biology of the Cell
- Published
- 2008-03
- Volume
- 19
- Issue
- 3
- Pages
- 1210-1219
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC2262963
- OpenAlex
- W2145650048
- Cited by
- 106
- References
- 64
- Citations by year
- 2024: 1 · 2023: 4 · 2022: 1 · 2021: 5 · 2020: 2 · 2019: 1 · 2018: 6 · 2017: 4 · 2016: 3 · 2015: 9 · 2014: 11 · 2013: 9 · 2012: 8
- FWCI
- 5.71
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Biology of the Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Canadian Institutes of Health Research
- National Center for Research Resources (P20RR16467-05, P20RR016467)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- SIRT1, NAD+-dependent deacetylase, growth inhibition, nutrient sensing, AMPK, telomerase activity, hTERT, cell immortalization, hematopoietic stem cells, glucose limitation, lifespan, NAD+ metabolism, shRNA knockdown
- MeSH terms
- Animals, Cell Line, Cell Survival, Food, Glucose, Hematopoietic Stem Cells, Humans, Multienzyme Complexes, Protein Serine-Threonine Kinases, Telomerase, Sirtuins, Cell Proliferation, Mice, AMP-Activated Protein Kinases, Sirtuin 1
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