Phosphofructokinase 1 glycosylation regulates cell growth and metabolism

W Yi, PM Clark, DE Mason, MC Keenan, C Hill… - Science, 2012 - science.org
W Yi, PM Clark, DE Mason, MC Keenan, C Hill, WA Goddard III, EC Peters, EM Driggers…
Science, 2012science.org
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 …
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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