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          Institute: MPI für molekulare Genetik     Collection: Department of Vertebrate Genomics     Display Documents



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ID: 411289.0, MPI für molekulare Genetik / Department of Vertebrate Genomics
A catabolic block does not sufficiently explain how 2-deoxy-d-glucose inhibits cell growth
Authors:Ralser, Markus; Wamelink, Mirjam M.; Struys, Eduard A.; Joppich, Christian; Krobitsch, Sylvia; Jakobs, Cornelis; Lehrach, Hans
Language:English
Date of Publication (YYYY-MM-DD):2008-11-18
Title of Journal:Proceedings of the National Academy of Sciences of the United States of America (Washington, DC)
Journal Abbrev.:Proc Natl Acad Sci U S A
Volume:105
Issue / Number:46
Start Page:17807
End Page:17811
Copyright:©2008 by the National Academy of Sciences
Review Status:not specified
Audience:Experts Only
Abstract / Description:The glucose analogue 2-deoxy-d-glucose (2-DG) restrains growth of normal and malignant cells, prolongs the lifespan of C. elegans, and is widely used as a glycolytic inhibitor to study metabolic activity with regard to cancer, neurodegeneration, calorie restriction, and aging. Here, we report that separating glycolysis and the pentose phosphate pathway highly increases cellular tolerance to 2-DG. This finding indicates that 2-DG does not block cell growth solely by preventing glucose catabolism. In addition, 2-DG provoked similar concentration changes of sugar-phosphate intermediates in wild-type and 2-DG-resistant yeast strains and in human primary fibroblasts. Finally, a genome-wide analysis revealed 19 2-DG-resistant yeast knockouts of genes implicated in carbohydrate metabolism and mitochondrial homeostasis, as well as ribosome biogenesis, mRNA decay, transcriptional regulation, and cell cycle. Thus, processes beyond the metabolic block are essential for the biological properties of 2-DG.
Free Keywords:Cell growth inhibition, Glycolysis, Off-target effect, Pentose phosphate pathway, Carbohydrate metabolism
External Publication Status:published
Document Type:Article
Communicated by:Hans Lehrach
Affiliations:MPI für molekulare Genetik
External Affiliations:Department of Clinical Chemistry, Metabolic Unit, VU Medical Center, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
Identifiers:ISSN:1091-6490 [eISSN]
DOI:10.1073/pnas.0803090105
URL:http://www.pnas.org/content/105/46/17807.full.pdf+...
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