Files and links (1)
Accepted (AM)Open Access (License Unspecified), Open
Journal article
Phosphofructokinase 1 glycosylation regulates cell growth and metabolism
Science (American Association for the Advancement of Science), v 337(6097), pp 975-980
24 Aug 2012
PMID: 22923583
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
Metrics
Details
- Title
- Phosphofructokinase 1 glycosylation regulates cell growth and metabolism
- Creators
- Wen Yi - Howard Hughes Medical InstitutePeter M Clark - Howard Hughes Medical InstituteDaniel E Mason - Genomics Institute of the Novartis Research FoundationMarie C Keenan - Agios Pharmaceuticals (United States)Collin Hill - Agios Pharmaceuticals (United States)William A Goddard, 3rdEric C Peters - Genomics Institute of the Novartis Research FoundationEdward M Driggers - Agios Pharmaceuticals (United States)Linda C Hsieh-Wilson - Howard Hughes Medical Institute
- Publication Details
- Science (American Association for the Advancement of Science), v 337(6097), pp 975-980
- Publisher
- American Association for the Advancement of Science (AAAS)
- Grant note
- Howard Hughes Medical Institute R01 GM084724 / NIGMS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; Drexel University
- Web of Science ID
- WOS:000307807600048
- Scopus ID
- 2-s2.0-84865300414
- Other Identifier
- 991019356345204721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology