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

S Basu, NF Totty, MS Irwin, M Sudol, J Downward - Molecular cell, 2003 - cell.com
S Basu, NF Totty, MS Irwin, M Sudol, J Downward
Molecular cell, 2003cell.com
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 …
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.
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