Millipore Home

• Home
• Products
• Services
• Learning Center
• Tech Library
• Support
• Company

Product Reference

SIRT1 acts as a nutrient-sensitive growth suppressor and its loss is associated with increased AMPK and telomerase activity.

Author	Swami R Narala, Richard C Allsopp, Trystan B Wells, Guanglei Zhang, Prerna Prasad, Matthew J Coussens, Derrick J Rossi, Irving L Weissman, Homayoun Vaziri
Citation Information	Molecular biology of the cell, 19:1210-9 (2008)
Keywords	AMP-Activated Protein Kinases, Animals, Cell Line, Cell Proliferation, Cell Survival, Food, Glucose, Hematopoietic Stem Cells, Humans, Mice, Multienzyme Complexes, Protein-Serine-Threonine Kinases, Sirtuins, Telomerase
Related Products	06-866
Pub Med ID	18184747

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.