Autoacetylation regulates P/CAF nuclear localization.
Acetylation is a posttranslational modification that alters the biological activities of proteins by affecting their association with other proteins or DNA, their catalytic activities, or their subcellular distribution. The acetyltransferase P/CAF is autoacetylated and acetylated by p300 in vivo. P/CAF autoacetylation is an intramolecular or intermolecular event. Intramolecular acetylation targets five lysines within the nuclear localization signal at the P/CAF C terminus. We analyzed how the subcellular distribution of P/CAF is regulated by intramolecular autoacetylation and found that a P/CAF mutant lacking histone acetyltransferase activity accumulated primarily in the cytoplasm. This cytoplasmic fraction of P/CAF is enriched for nonautoacetylated P/CAF. In addition, P/CAF deacetylation by HDAC3 and in a minor degree by HDAC1, HDAC2, or HDAC4 leads to cytoplasmic accumulation of P/CAF. Importantly, our data show that P/CAF accumulates in the cytoplasm during apoptosis. These results reveal the molecular mechanism of autoacetylation control of P/CAF nuclear translocation and suggest a novel pathway by which P/CAF activity is controlled in vivo.
Blanco-García
Noemí
N
Instituto de Biología Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Baldiri i Reixac 15-21, Parc Cientific de Barcelona, E-08028 Barcelona, Spain.
Asensio-Juan
Elena
E
de la Cruz
Xavier
X
Martínez-Balbás
Marian A
MA
D000107:Acetylation; D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002467:Cell Nucleus / Q000201:enzymology* / Q000235:genetics; D003593:Cytoplasm / Q000201:enzymology* / Q000235:genetics; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D009154:Mutation; D041681:NIH 3T3 Cells; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
D051548:Histone Acetyltransferases; D019913:Nuclear Localization Signals; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor