Yap1 phosphorylation by c-Abl is a critical step in selective activation of proapoptotic genes in response to DNA damage.

Cells undergo apoptosis upon exposure to severe DNA damage stress. Under this condition, p73 is phosphorylated and activated by c-Abl. The transcription coactivator Yap1 binds p73 to generate a complex that escapes p73 proteasomal degradation and recruits p300 to support transcription of proapoptotic genes. However, the mechanism of selective activation ...
of proapoptotic genes by Yap1 remained unclear. In this study, we show that c-Abl directly phosphorylates Yap1 at position Y357 in response to DNA damage. Tyrosine-phosphorylated Yap1 is a more stable protein that displays higher affinity to p73 and selectively coactivates p73 proapoptotic target genes. Furthermore, we show that Yap1 switches between p73-mediated proapoptotic and growth arrest target genes based on its phosphorylation state. Thus, our data demonstrate that modification of a transcription coactivator, namely the DNA damage-induced phosphorylation of Yap1 by c-Abl, influences the specificity of target gene activation.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Apoptosis, Benzamides, Cell Line, Cell Line, Tumor, Cisplatin, Cycloheximide, DNA Damage, DNA-Binding Proteins, Gamma Rays, HCT116 Cells, Half-Life, HeLa Cells, Humans, Kidney, Kinetics, Nuclear Proteins, Phosphoproteins, Phosphorylation, Piperazines, Plasmids, Protein Structure, Tertiary, Protein Synthesis Inhibitors, Proto-Oncogene Proteins c-abl, Pyrimidines, RNA, Messenger, Transfection, Tumor Suppressor Proteins, Tyrosine
Mol. Cell
Date: Feb. 15, 2008
Download Curated Data For This Publication
167312
Switch View:
  • Interactions 5