Abstract:
: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.
journal_name
Mol Celljournal_title
Molecular cellauthors
Levy D,Adamovich Y,Reuven N,Shaul Ydoi
10.1016/j.molcel.2007.12.022subject
Has Abstractpub_date
2008-02-15 00:00:00pages
350-61issue
3eissn
1097-2765issn
1097-4164pii
S1097-2765(08)00064-6journal_volume
29pub_type
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