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Calendar Name: seminars
Scheduled for: Tuesday, May 8 2012, 14:00 - 15:30
Event text:    Prof Salvador Moncada
	       
	       Wolfson Institute for Biomedical Research
	       University College London
	       
	       London
	       UNITED KINGDOM
Details:       “Connecting cell cycle progression to metabolic
	       requirements”
	       
	       ABSTRACT
	       Cell proliferation is accompanied by an increase in the
	       utilization of glucose and glutamine. The proliferative
	       response is dependent on a decrease in the activity of
	       the ubiquitin ligase anaphase-promoting
	       complex/cyclosome (APC/C)-Cdh1 which controls G1-
	       to-S-phase transition by targeting degradation motifs,
	       including the KEN box. This occurs not only in cell
	       cycle proteins but also in the glycolysis-promoting
	       enzyme
	       6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
	       isoform 3 (PFKFB3), as we have demonstrated in cells in
	       culture as well as in proliferating human T lymphocytes.
	       Moreover, we have found that glutaminase 1 is a
	       substrate for this ubiquitin ligase and appears at the
	       same time as PFKFB3 in proliferating cells. Glutaminase
	       1 is the first enzyme in glutaminolysis and converts
	       glutamine to glutamate, yielding intermediates for cell
	       proliferation. Thus APC/C-Cdh1 is responsible for the
	       increased utilization not only of glucose but also of
	       glutamine and, as such, accounts for the critical step
	       that links the cell cycle with the metabolic substrates
	       essential for its progression. A further degree of
	       control is provided by a second ubiquitin ligase – SCF
	       (Skp1/CUL-1/F-box protein)--TrCP – which causes
	       the disappearance of PFKFB3 during late G1/S. Thus the
	       presence of PFKFB3 is tightly controlled to ensure the
	       upregulation of glycolysis at a specific point in G1.
	       The relevance of these observations to understanding of
	       the proliferative and metabolic changes that occur in
	       normal and in cancer cells will be discussed.

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