Jack of All Trades

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Science  14 May 2010:
Vol. 328, Issue 5980, pp. 795
DOI: 10.1126/science.328.5980.795-b

The efficiency with which organisms operate compels many proteins to function in more than one way and often at more than one location. TAZ is a protein that acts with other proteins to regulate transcription in response to activation of the Hippo signal transduction pathway, which controls cell proliferation and organ size, and TAZ can move between the nucleus and the cytoplasm; but that's not all. Varelas et al. looked for genes that influence signaling by the Wnt proteins, which are secreted morphogens that control proliferation and cell fate in developing tissues, and found TAZ. Mice lacking TAZ showed increased levels of the Wnt-dependent transcriptional regulator β-catenin in both the cytoplasm and nucleus of kidney cells. TAZ interacted directly with the Dishevelled protein—a component of the Wnt signaling pathway—and depletion of TAZ or inhibition of Hippo signaling increased Wnt signaling in cultured cells. The Hippo pathway protein kinase LATS1 inhibits TAZ function by phosphorylation; interfering with this step diminished Wnt-dependent transcription. TAZ has also been implicated in signaling by transforming growth factor–β. Add to this the identification of TAZ as a component of a ubiquitin ligase complex that degrades an ion channel, and you have one busy protein indeed.

Dev. Cell 18, 579 (2010).

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