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Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/121770

Degradation of cyclin A is regulated by acetylation

AutorMateo, Francesca ; Vidal-Laliena, Miriam; Canela, Núria; Busino, Luca; Martínez-Balbás, Marian ; Pagano, Michele; Agell, Neus; Bachs, Oriol
Fecha de publicación1-jun-2009
EditorNature Publishing Group
CitaciónOncogene 28(29): 2654-2666 (2009)
ResumenCyclin A accumulates at the onset of S phase, remains high during G 2 and early mitosis and is degraded at prometaphase. Here, we report that the acetyltransferase P/CAF directly interacts with cyclin A that as a consequence becomes acetylated at lysines 54, 68, 95 and 112. Maximal acetylation occurs simultaneously to ubiquitylation at mitosis, indicating importance of acetylation on cyclin A stability. This was further confirmed by the observation that the pseudoacetylated cyclin A mutant can be ubiquitylated whereas the nonacetylatable mutant cannot. The nonacetylatable mutant is more stable than cyclin A WT (cycA WT) and arrests cell cycle at mitosis. Moreover, in cells treated with histone deacetylase inhibitors cyclin A acetylation increases and its stability decreases, thus supporting the function of acetylation on cyclin A degradation. Although the nonacetylatable mutant cannot be ubiquitylated, it interacts with the proteins needed for its degradation (cdks, Cks, Cdc20, Cdh1 and APC/C). In fact, its association with cdks is increased and its complexes with these kinases display higher activity than control cycA WT-cdk complexes. All these results indicate that cyclin A acetylation at specific lysines is crucial for cyclin A stability and also has a function in the regulation of cycA-cdk activity. © 2009 Macmillan Publishers Limited All rights reserved.
Versión del editorhttp://dx.doi.org/10.1038/onc.2009.127
Identificadoresdoi: 10.1038/onc.2009.127
issn: 0950-9232
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