Publication Date:
2012-10-16
Description:
Cancer cells exhibit several unique metabolic phenotypes that are critical for cell growth and proliferation. Specifically, they overexpress the M2 isoform of the tightly regulated enzyme pyruvate kinase (PKM2), which controls glycolytic flux, and are highly dependent on de novo biosynthesis of serine and glycine. Here we describe a new rheostat-like mechanistic relationship between PKM2 activity and serine biosynthesis. We show that serine can bind to and activate human PKM2, and that PKM2 activity in cells is reduced in response to serine deprivation. This reduction in PKM2 activity shifts cells to a fuel-efficient mode in which more pyruvate is diverted to the mitochondria and more glucose-derived carbon is channelled into serine biosynthesis to support cell proliferation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894725/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894725/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chaneton, Barbara -- Hillmann, Petra -- Zheng, Liang -- Martin, Agnes C L -- Maddocks, Oliver D K -- Chokkathukalam, Achuthanunni -- Coyle, Joseph E -- Jankevics, Andris -- Holding, Finn P -- Vousden, Karen H -- Frezza, Christian -- O'Reilly, Marc -- Gottlieb, Eyal -- A12477/Cancer Research UK/United Kingdom -- Cancer Research UK/United Kingdom -- England -- Nature. 2012 Nov 15;491(7424):458-62. doi: 10.1038/nature11540. Epub 2012 Oct 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research UK, The Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, Scotland, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23064226" target="_blank"〉PubMed〈/a〉
Keywords:
Cell Line, Tumor
;
Cell Proliferation
;
Enzyme Activation/drug effects
;
Enzyme Activators/pharmacology
;
Glucose/metabolism
;
Glycine/metabolism/pharmacology
;
Humans
;
*Ligands
;
Pyruvate Kinase/genetics/*metabolism
;
Pyruvic Acid/metabolism
;
Recombinant Proteins/metabolism
;
Serine/*metabolism/pharmacology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
