PKB/Akt phosphorylates the CDC25B phosphatase and regulates its intracellular localisation.
Regulation of the intracellular localisation of its actors is one of the key mechanisms underlying cell cycle control. CDC25 phosphatases are activators of Cyclin-Dependent Kinases (CDK) that undergo nucleo-cytoplasmic shuttling during the cell cycle and in response to checkpoint activation. Here we report that the protein kinase PKB/Akt phosphorylates CDC25B on serine 353, resulting in a nuclear export-dependent cytoplasmic accumulation of the phosphatase. Oxidative stress activates PKB/Akt and reproduces the effect on CDC25B phosphorylation and localisation. However, inhibition of PKB/Akt activity only partially reverted the effect of oxidative stress on CDC25B localisation and mutation of serine 353 abolishes phosphorylation but only delays nuclear exclusion. These results indicate that additional mechanisms are also involved in preventing nuclear import of CDC25B. Our findings identify CDC25B as a target of PKB/Akt and provide new insight into the regulation of its localisation in response to stress-activated signalling pathways.
Baldin
Véronique
V
LBCMCP-CNRS UMR5088- IFR109 Université Paul Sabatier, 118 route de Narbonne, 31062 Toulouse, France.
Theis-Febvre
Nathalie
N
Benne
Clarisse
C
Froment
Carine
C
Cazales
Martine
M
Burlet-Schiltz
Odile
O
Ducommun
Bernard
B
D064413:3-Phosphoinositide-Dependent Protein Kinases; D000818:Animals; D018797:Cell Cycle Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D028884:Karyopherins / Q000502:physiology; D019913:Nuclear Localization Signals / Q000502:physiology; D018384:Oxidative Stress; D010957:Plasmids; D017354:Point Mutation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins / Q000235:genetics; D020687:cdc25 Phosphatases / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D000097606:Exportin 1 Protein
D064413:3-Phosphoinositide-Dependent Protein Kinases; D018797:Cell Cycle Proteins; D006861:Hydrogen Peroxide; D028884:Karyopherins; D019913:Nuclear Localization Signals; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D020687:cdc25 Phosphatases; D000097606:Exportin 1 Protein; C494918:AKT1 protein, human; C517008:CDC25B protein, human