Akt phosphorylates the Yes-associated protein, YAP, to induce interaction with 14-3-3 and attenuation of p73-mediated apoptosis.

We have used an affinity purification method to identify substrates of protein kinase B/Akt. One protein that associates with 14-3-3 in an Akt-dependent manner is shown here to be the Yes-associated protein (YAP), which is phosphorylated by Akt at serine 127, leading to binding to 14-3-3. Akt promotes YAP localization ...
to the cytoplasm, resulting in loss from the nucleus where it functions as a coactivator of transcription factors including p73. p73-mediated induction of Bax expression following DNA damage requires YAP function and is attenuated by Akt phosphorylation of YAP. YAP overexpression increases, while YAP depletion decreases, p73-mediated apoptosis following DNA damage, in an Akt inhibitable manner. Akt phosphorylation of YAP may thus suppress the induction of the proapoptotic gene expression response following cellular damage.
Mesh Terms:
14-3-3 Proteins, Adaptor Proteins, Signal Transducing, Amino Acid Motifs, Animals, Antibodies, Apoptosis, Carrier Proteins, Cell Line, DNA-Binding Proteins, Fluorescent Dyes, Genes, Reporter, Genes, Tumor Suppressor, Green Fluorescent Proteins, Humans, Luminescent Proteins, Nuclear Proteins, Phosphoproteins, Phosphorylation, Protein Binding, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, RNA Interference, Recombinant Fusion Proteins, Serine, Transcription, Genetic, Tumor Suppressor Proteins, Tyrosine 3-Monooxygenase
Mol. Cell
Date: Jan. 01, 2003
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