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

Mol Cell. 2003 Jan;11(1):11-23. doi: 10.1016/s1097-2765(02)00776-1.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins
  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Motifs
  • Animals
  • Antibodies / metabolism
  • Apoptosis / physiology*
  • Carrier Proteins / metabolism*
  • Cell Line
  • DNA-Binding Proteins / metabolism*
  • Fluorescent Dyes / metabolism
  • Genes, Reporter
  • Genes, Tumor Suppressor
  • Green Fluorescent Proteins
  • Humans
  • Luminescent Proteins / metabolism
  • Nuclear Proteins / metabolism*
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • RNA Interference
  • Recombinant Fusion Proteins / metabolism
  • Serine / metabolism
  • Transcription Factors
  • Transcription, Genetic
  • Tumor Protein p73
  • Tumor Suppressor Proteins
  • Tyrosine 3-Monooxygenase / isolation & purification
  • Tyrosine 3-Monooxygenase / metabolism*

Substances

  • 14-3-3 Proteins
  • Adaptor Proteins, Signal Transducing
  • Antibodies
  • Carrier Proteins
  • DNA-Binding Proteins
  • Fluorescent Dyes
  • Luminescent Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • Transcription Factors
  • Tumor Protein p73
  • Tumor Suppressor Proteins
  • YAP1 (Yes-associated) protein, human
  • p73 protein, human
  • Green Fluorescent Proteins
  • Serine
  • Tyrosine 3-Monooxygenase
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt