For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
79
views
71
references
 Top references
cited by
82
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      88
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      Stressin' Sestrins take an aging fight

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Sestrins (Sesns) are a family of highly conserved stress-responsive proteins, transcriptionally regulated by p53 and forkhead transcription factor that exhibit oxidoreductase activity in vitro and can protect cells from oxidative stress. However, their major biochemical and physiological function does not appear to depend on their redox (reduction and oxidation) activity. Sesns promote activation of adenosine-5′-monophosphate (AMP)-dependent protein kinase in both mammals and flies. Stress-induced Sesn expression results in inhibition of the target of rapamycin complex 1 (TORC1) and the physiological and pathological implications of disrupting the Sesns-TORC1 crosstalk are now being unravelled. Detailing their mechanism of action and exploring their roles in human physiology point to exciting new insights to topics as diverse as stress, cancer, metabolism and aging.

          Related collections

          Most cited references71

          • Record: found
          • Abstract: found
          • Article: not found

          Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours.

          L A Donehower, M. Harvey, B Slagle … (1992)
          Mutations in the p53 tumour-suppressor gene are the most frequently observed genetic lesions in human cancers. To investigate the role of the p53 gene in mammalian development and tumorigenesis, a null mutation was introduced into the gene by homologous recombination in murine embryonic stem cells. Mice homozygous for the null allele appear normal but are prone to the spontaneous development of a variety of neoplasms by 6 months of age. These observations indicate that a normal p53 gene is dispensable for embryonic development, that its absence predisposes the animal to neoplastic disease, and that an oncogenic mutant form of p53 is not obligatory for the genesis of many types of tumours.
          Article 0 comments Cited 705 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found

            TIGAR, a p53-Inducible Regulator of Glycolysis and Apoptosis

            Karim Bensaad, Atsushi Tsuruta, Mary A. Selak … (2006)
            The p53 tumor-suppressor protein prevents cancer development through various mechanisms, including the induction of cell-cycle arrest, apoptosis, and the maintenance of genome stability. We have identified a p53-inducible gene named TIGAR (TP53-induced glycolysis and apoptosis regulator). TIGAR expression lowered fructose-2,6-bisphosphate levels in cells, resulting in an inhibition of glycolysis and an overall decrease in intracellular reactive oxygen species (ROS) levels. These functions of TIGAR correlated with an ability to protect cells from ROS-associated apoptosis, and consequently, knockdown of endogenous TIGAR expression sensitized cells to p53-induced death. Expression of TIGAR may therefore modulate the apoptotic response to p53, allowing survival in the face of mild or transient stress signals that may be reversed or repaired. The decrease of intracellular ROS levels in response to TIGAR may also play a role in the ability of p53 to protect from the accumulation of genomic damage.
            Article 0 comments Cited 642 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway.

              Pankaj Kapahi, Brian M. Zid, Tony Harper … (2004)
              In many species, reducing nutrient intake without causing malnutrition extends lifespan. Like DR (dietary restriction), modulation of genes in the insulin-signaling pathway, known to alter nutrient sensing, has been shown to extend lifespan in various species. In Drosophila, the target of rapamycin (TOR) and the insulin pathways have emerged as major regulators of growth and size. Hence we examined the role of TOR pathway genes in regulating lifespan by using Drosophila. We show that inhibition of TOR signaling pathway by alteration of the expression of genes in this nutrient-sensing pathway, which is conserved from yeast to human, extends lifespan in a manner that may overlap with known effects of dietary restriction on longevity. In Drosophila, TSC1 and TSC2 (tuberous sclerosis complex genes 1 and 2) act together to inhibit TOR (target of rapamycin), which mediates a signaling pathway that couples amino acid availability to S6 kinase, translation initiation, and growth. We find that overexpression of dTsc1, dTsc2, or dominant-negative forms of dTOR or dS6K all cause lifespan extension. Modulation of expression in the fat is sufficient for the lifespan-extension effects. The lifespan extensions are dependent on nutritional condition, suggesting a possible link between the TOR pathway and dietary restriction.
              Article 0 comments Cited 448 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): EMBO Mol Med
                Journal ID (iso-abbrev): EMBO Mol Med
                Journal ID (publisher-id): emmm
                Title: EMBO Molecular Medicine
                Publisher: WILEY-VCH Verlag (Weinheim )
                ISSN (Print): 1757-4676
                ISSN (Electronic): 1757-4684
                Publication date (Print): October 2010
                Volume: 2
                Issue: 10
                Pages: 388-400
                Affiliations
                simpleLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California San Diego, CA, USA
                Author notes
                * Corresponding author: Tel: +1 858 534 1361; Fax: +1 858 534 8158 E-mail: karinoffice@ 123456ucsd.edu
                Article
                DOI: 10.1002/emmm.201000097
                PMC ID: 3166214
                PubMed ID: 20878915
                SO-VID: 24c3ff65-a651-4925-8fbd-628faffbf368
                Copyright © Copyright © 2010 EMBO Molecular Medicine
                History
                Date received : 24 June 2010
                Date revision received : 11 August 2010
                Date accepted : 20 August 2010
                Categories
                Subject: Review

                ScienceOpen disciplines: Molecular medicine
                Keywords: target of rapamycin,aging,sestrin,p53,redox
                Data availability:
                ScienceOpen disciplines: Molecular medicine
                Keywords: target of rapamycin, aging, sestrin, p53, redox

                Comments

                Comment on this article

                scite_

                Similar content88

                See all similar

                Cited by81

                See all cited by

                Most referenced authors3,109

                See all reference authors