Below is an abstract from the PNAS web site (www.pnas.org), emphasis mine. This article was mentioned in the May Nature Biotechnology, p412. My NBt's come later than you guys':-) Article mentions that Seattle based Cytokine Networks plans to develop treatments that target iPFK-2.
Jason
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PNAS Vol. 96, Issue 6, 3047-3052, March 16, 1999
Medical Sciences
An inducible gene product for
6-phosphofructo-2-kinase with an
AU-rich instability element: Role in
tumor cell glycolysis and the Warburg
effect
(phosphofructokinase / fructose 2,6-bisphosphate / cancer / oncogenesis)
Jason Chesney, Robert Mitchell, Fabio Benigni, Michael Bacher, Lori Spiegel, Yousef Al-Abed,
Jung Hee Han, Christine Metz, and Richard Bucala*
Laboratory of Medical Biochemistry, Picower Institute for Medical Research, 350 Community Drive,
Manhasset, NY 11030
Communicated by George J. Todaro, University of Washington, Seattle, WA, January 6, 1999 (received
for review October 12, 1998)
Cancer cells maintain a high glycolytic rate even in the presence of oxygen, a phenomenon first described
over 70 years ago and known historically as the Warburg effect. Fructose 2,6-bisphosphate is a powerful
allosteric regulator of glycolysis that acts to stimulate the activity of 6-phosphofructo-1-kinase (PFK-1),
the most important control point in mammalian glycolysis. The steady state concentration of fructose
2,6-bisphosphate in turn depends on the activity of the enzyme 6-phosphofructo-2-kinase
(PFK-2)/fructose-2,6-bisphosphatase, which is expressed in several tissue-specific isoforms. We report
herein the identification of a gene product for this enzyme that is induced by proinflammatory stimuli and
which is distinguished by the presence of multiple copies of the AUUUA mRNA instability motif in its
3'-untranslated end. This inducible gene for PFK-2 is expressed constitutively in several human cancer cell
lines and was found to be required for tumor cell growth in vitro and in vivo. Inhibition of inducible
PFK-2 protein expression decreased the intracellular level of 5-phosphoribosyl-1-pyrophosphate, a
product of the pentose phosphate pathway and an important precursor for nucleic acid biosynthesis.
These studies identify a regulatory isoenzyme that may be essential for tumor growth and provide an
explanation for long-standing observations concerning the apparent coupling of enhanced glycolysis and
cell proliferation. |
