Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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14-3-3 Proteins
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Adaptor Proteins, Signal Transducing*
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Amino Acid Motifs
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Animals
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Antibodies / metabolism
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Apoptosis / physiology*
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Carrier Proteins / metabolism*
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Cell Line
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DNA-Binding Proteins / metabolism*
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Fluorescent Dyes / metabolism
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Genes, Reporter
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Genes, Tumor Suppressor
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Green Fluorescent Proteins
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Humans
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Luminescent Proteins / metabolism
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Nuclear Proteins / metabolism*
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Phosphoproteins / metabolism*
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Phosphorylation
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Protein Binding
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-akt
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RNA Interference
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Recombinant Fusion Proteins / metabolism
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Serine / metabolism
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Transcription Factors
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Transcription, Genetic
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Tumor Protein p73
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Tumor Suppressor Proteins
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Tyrosine 3-Monooxygenase / isolation & purification
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Tyrosine 3-Monooxygenase / metabolism*
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YAP-Signaling Proteins
Substances
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14-3-3 Proteins
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Adaptor Proteins, Signal Transducing
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Antibodies
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Carrier Proteins
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DNA-Binding Proteins
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Fluorescent Dyes
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Luminescent Proteins
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Nuclear Proteins
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Phosphoproteins
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Proto-Oncogene Proteins
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Recombinant Fusion Proteins
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TP73 protein, human
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Transcription Factors
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Tumor Protein p73
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Tumor Suppressor Proteins
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YAP-Signaling Proteins
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YAP1 protein, human
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Green Fluorescent Proteins
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Serine
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Tyrosine 3-Monooxygenase
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AKT1 protein, human
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt