Autoacetylation regulates P/CAF nuclear localization

  1. Noemí Blanco-García 1
  2. Elena Asensio-Juan 1
  3. Xavier de la Cruz 1
  4. Marian A Martínez-Balbás 1
  1. 1 Consejo Superior de Investigaciones Científicas
    info

    Consejo Superior de Investigaciones Científicas

    Madrid, España

    ROR https://ror.org/02gfc7t72

Revista:
Journal of Biological Chemistry

Año de publicación: 2009

Volumen: 284

Páginas: 1342-1352

Tipo: Artículo

Resumen

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.

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