UV-induced downregulation of the CDC25B protein in human cells.
The CDC25B phosphatase regulates the activation of CDK1-Cyclin B at the onset of mitosis, being a key target of the checkpoint pathways activated by cellular stress and DNA damage. Previous work has reported that checkpoint activation induces the sequestration of CDC25B in the cytoplasm. Here we show that in response to UV irradiation, the levels of CDC25B protein can be downregulated independently of classical checkpoints pathways such as p53, ATM/ATR and p38 MAPK. We also show that translational repression mediated by eIF2alpha phosphorylation regulates CDC25B expression levels. Taken together, our results illustrate a new mechanism of CDC25B regulation in response to stress.
Lemaire
Matthieu
M
CNIO (Spanish National Cancer Center), Melchor Fernandez Almagro 3, Madrid, Spain.
Ducommun
Bernard
B
Nebreda
Angel R
AR
D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000502:physiology; D002477:Cells / Q000378:metabolism* / Q000528:radiation effects*; D004268:DNA-Binding Proteins / Q000502:physiology; D015536:Down-Regulation / Q000528:radiation effects; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D014176:Protein Biosynthesis / Q000528:radiation effects; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology / Q000528:radiation effects; D013312:Stress, Physiological / Q000502:physiology / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000502:physiology; D014466:Ultraviolet Rays; D020687:cdc25 Phosphatases / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C517008:CDC25B protein, human; D020687:cdc25 Phosphatases