Research ArticleCell Biology

Ajuba Family Proteins Link JNK to Hippo Signaling

Sci. Signal.  10 Sep 2013:
Vol. 6, Issue 292, pp. ra81
DOI: 10.1126/scisignal.2004324

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Shutting Down Hippo

The Hippo pathway exerts tumor-suppressive effects by inhibiting the transcriptional coactivator Yorkie (Yki) in Drosophila or YAP in mammals. c-Jun N-terminal kinase (JNK) can promote proliferation in response to injury and has been linked to activation of Yki and YAP. Sun and Irvine found that the Ajuba family of proteins enabled JNK to stimulate the activity of Yki and YAP. In Drosophila, the growth of tumors dependent on JNK and Yki activation was reduced by ablation of Jub (also known as Ajuba LIM protein). In mammalian cells, JNK activation decreased the activity of LATS1, a kinase that phosphorylates and inhibits YAP, and enhanced the association of LATS1 with various Ajuba family proteins in a manner dependent on phosphorylation of the Ajuba proteins. These results suggest a model in which JNK-mediated phosphorylation of Ajuba proteins inhibits the Hippo pathway and thus stimulates the transcriptional activation of genes that promote proliferation.