TY - JOUR
T1 - Anaphase-promoting complex/cyclosome-Cdh1 coordinates glycolysis and glutaminolysis with transition to S phase in human T lymphocytes
AU - Colombo, Sergio L.
AU - Palacios-Callender, Miriam
AU - Frakich, Nanci
AU - De Leon, Joel
AU - Schmitt, Christoph A.
AU - Boorn, Leanne
AU - Davis, Nicola
AU - Moncada, Salvador
N1 - Colombo, Sergio L Palacios-Callender, Miriam Frakich, Nanci De Leon, Joel Schmitt, Christoph A Boorn, Leanne Davis, Nicola Moncada, Salvador 086729/Wellcome Trust/United Kingdom 36801/Biotechnology and Biological Sciences Research Council/United Kingdom Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):18868-73. doi: 10.1073/pnas.1012362107. Epub 2010 Oct 4.
PY - 2010/11/2
Y1 - 2010/11/2
N2 - 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 anaphasepromoting complex/cyclosome (APC/C)-Cdh1 which controls G1-to-S-phase transition by targeting degradation motifs, notably 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 recently demonstrated in cells in culture. We now show that APC/C-Cdh1 controls the proliferative response of 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 T lymphocytes. Glutaminase 1 is the first enzyme in glutaminolysis, which converts glutamine to lactate, yielding intermediates for cell proliferation. Thus APC/C-Cdh1 is responsible for the provision 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.
AB - 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 anaphasepromoting complex/cyclosome (APC/C)-Cdh1 which controls G1-to-S-phase transition by targeting degradation motifs, notably 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 recently demonstrated in cells in culture. We now show that APC/C-Cdh1 controls the proliferative response of 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 T lymphocytes. Glutaminase 1 is the first enzyme in glutaminolysis, which converts glutamine to lactate, yielding intermediates for cell proliferation. Thus APC/C-Cdh1 is responsible for the provision 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.
KW - 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3
KW - Cell cycle
KW - Glutaminase
KW - Proliferation
U2 - 10.1073/pnas.1012362107
DO - 10.1073/pnas.1012362107
M3 - Article
SN - 0027-8424
VL - 107
SP - 18868
EP - 18873
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 44
ER -