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  A catabolic block does not sufficiently explain how 2-deoxy-d-glucose inhibits cell growth

Ralser, M., Wamelink, M. M., Struys, E. A., Joppich, C., Krobitsch, S., Jakobs, C., et al. (2008). A catabolic block does not sufficiently explain how 2-deoxy-d-glucose inhibits cell growth. Proceedings of the National Academy of Sciences of the United States of America (Washington, DC), 105(46), 17807-17811. doi:10.1073/pnas.0803090105.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7EAE-7 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7EAF-5
Genre: Journal Article
Alternative Title : Proc Natl Acad Sci U S A

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 Creators:
Ralser, Markus1, Author              
Wamelink, Mirjam M., Author
Struys, Eduard A., Author
Joppich, Christian2, Author
Krobitsch, Sylvia3, Author              
Jakobs, Cornelis, Author
Lehrach, Hans1, Author              
Affiliations:
1Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              
2Max Planck Society, ou_persistent13              
3Neurodegenerative Disorders (Sylvia Krobitsch), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479661              

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Free keywords: Cell growth inhibition, Glycolysis, Off-target effect, Pentose phosphate pathway, Carbohydrate metabolism
 Abstract: 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.

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Language(s): eng - English
 Dates: 2008-11-18
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Degree: -

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Title: Proceedings of the National Academy of Sciences of the United States of America (Washington, DC)
  Alternative Title : Proc Natl Acad Sci U S A
Source Genre: Journal
 Creator(s):
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Publ. Info: -
Pages: - Volume / Issue: 105 (46) Sequence Number: - Start / End Page: 17807 - 17811 Identifier: ISSN: 1091-6490