Regulation of APC/C-Cdh1 and Its Function in Neuronal Survival |
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Authors: | Angeles Almeida |
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Institution: | 1. Instituto de Investigaci??n Biom??dica de Salamanca, Hospital Universitario de Salamanca, 37007, Salamanca, Spain 2. Departamento de Bioqu??mica y Biolog??a Molecular, Instituto de Neurociencias de Castilla y Le??n, Universidad de Salamanca, 37007, Salamanca, Spain 3. Research Unit, University Hospital of Salamanca, Edificio Departamental (Lab. 122), Plaza Doctores de la Reina, 37007, Salamanca, Spain
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Abstract: | Neurons are post-mitotic cells that undergo an active downregulation of cell cycle-related proteins to survive. The activity of the anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase that regulates cell cycle progression in proliferating cells, plays a relevant role in post-mitotic neurons. Recent advances in the study of the regulation of APC/C have documented that the APC/C-activating cofactor, Cdh1, is essential for the function(s) of APC/C in neuronal survival. Here, we review the normal regulation of APC/C activity in proliferating cells and neurons. We conclude that in neurons the APC/C-Cdh1 complex actively downregulates the stability of the cell cycle protein cyclin B1 and the glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3. Keeping these proteins destabilized is critical both for preventing the aberrant reentry of post-mitotic neurons into the cell cycle and for maintaining their reduced antioxidant status. Further understanding of the pathophysiological regulation of these proteins by APC/C-Cdh1 in neurons will be important for the search for novel therapeutic targets against neurodegeneration. |
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