Degradation of cyclin A is regulated by acetylation

Oncogene. 2009 Jul 23;28(29):2654-66. doi: 10.1038/onc.2009.127. Epub 2009 Jun 1.


Cyclin 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Cyclin A / genetics
  • Cyclin A / metabolism*
  • Cyclin-Dependent Kinase 2 / metabolism*
  • HeLa Cells
  • Humans
  • Lysine / genetics
  • Lysine / metabolism
  • Mutation
  • p300-CBP Transcription Factors / metabolism*


  • Cyclin A
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • Cyclin-Dependent Kinase 2
  • Lysine