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.
Pubmed ID: 12535517 RIS Download
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 Protein p73 | Tumor Suppressor Proteins | Tyrosine 3-Monooxygenase