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Título
Human Cdc14A regulates Wee1 stability by counteracting CDK-mediated phosphorylation
Autor(es)
Materia
Cell Cycle, Mitosis, Cdc14 phosphatase, CDK mitotic complexes
Clasificación UNESCO
2415 Biología Molecular
2407 Biología Celular
Bioquimica
Fecha de publicación
2012
Editor
American Society for Cell Biology
Citación
Ovejero, S., Ayala, P., Bueno, A., & Sacristán, M. P. (2012). Human Cdc14A regulates Wee1 stability by counteracting CDK-mediated phosphorylation. Molecular biology of the cell, 23(23), 4515-4525.
Resumen
[EN]The activity of Cdk1–cyclin B1 mitotic complexes is regulated by the balance between the counteracting activities of Wee1/Myt1 kinases and Cdc25 phosphatases. These kinases and phosphatases must be strictly regulated to ensure proper mitotic timing. One masterpiece of this regulatory network is Cdk1, which promotes Cdc25 activity and suppresses inhibitory Wee1/Myt1 kinases through direct phosphorylation. The Cdk1-dependent phosphorylation of Wee1 primes phosphorylation by additional kinases such as Plk1, triggering Wee1 degradation at the onset of mitosis. Here we report that Cdc14A plays an important role in the regulation of Wee1 stability. Depletion of Cdc14A results in a significant reduction in Wee1 protein levels. Cdc14A binds to Wee1 at its amino-terminal domain and reverses CDK-mediated Wee1 phosphorylation. In particular, we found that Cdc14A inhibits Wee1 degradation through the dephosphorylation of Ser-123 and Ser-139 residues. Thus the lack of phosphorylation of these two residues prevents the interaction with Plk1 and the consequent efficient Wee1 degradation at the onset of mitosis. These data support the hypothesis that Cdc14A counteracts Cdk1–cyclin B1 activity through Wee1 dephosphorylation.
URI
ISSN
1059-1524
DOI
10.1091/mbc.E12-04-0260
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