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Science. 2012 Aug 24;337(6097):975-80. doi: 10.1126/science.1222278.

Phosphofructokinase 1 glycosylation regulates cell growth and metabolism.

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  • 1Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.

Abstract

Cancer cells must satisfy the metabolic demands of rapid cell growth within a continually changing microenvironment. We demonstrated that the dynamic posttranslational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAcylation) is a key metabolic regulator of glucose metabolism. O-GlcNAcylation was induced at serine 529 of phosphofructokinase 1 (PFK1) in response to hypoxia. Glycosylation inhibited PFK1 activity and redirected glucose flux through the pentose phosphate pathway, thereby conferring a selective growth advantage on cancer cells. Blocking glycosylation of PFK1 at serine 529 reduced cancer cell proliferation in vitro and impaired tumor formation in vivo. These studies reveal a previously uncharacterized mechanism for the regulation of metabolic pathways in cancer and a possible target for therapeutic intervention.

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PMID:
22923583
[PubMed - indexed for MEDLINE]
PMCID:
PMC3534962
Free PMC Article

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