Editors' ChoiceDevelopment

TAZ, Jack of All Trades

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Science Signaling  04 May 2010:
Vol. 3, Issue 120, pp. ec132
DOI: 10.1126/scisignal.3120ec132

The efficiency with which living organisms operate dictates that many proteins have more than one function, often at more than one location in the cell. Results reported by Varelas et al. make us pause and wonder whether there is an upper limit on such “moonlighting,” as it is sometimes called. As the name suggests, the TAZ (transcriptional coactivator with PDZ binding motif) protein coordinates with other proteins to regulate transcription. It does so in response to activation of the Hippo signal transduction pathway, which controls cell proliferation and apoptosis and contributes to regulation of organ size. TAZ can move between the nucleus and cytoplasm, a process regulated by phosphorylation of TAZ and its consequent association with the protein 14-3-3. But that’s not all. The authors discovered TAZ in a multidimensional screen for genes whose products influence signaling by the Wnt proteins—secreted morphogens that control proliferation and cell fate in developing tissues. Depletion of TAZ from human embryonic kidney (HEK) 293 cells enhanced activity of a transcriptional reporter dependent on Wnt signaling. Knockout mice lacking TAZ showed increased abundance 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 markers of Wnt signaling in cultured cells. The Hippo pathway comprises a set of protein kinases, and one of these, LATS1, inhibits TAZ function by phosphorylation. Interfering with such control of TAZ by the Hippo pathway in HEK293 cells diminished Wnt-dependent transcription of a reporter gene. Studies in Drosophila confirmed that Wnt signaling during development was also inhibited through the Hippo pathway. Thus, the authors propose that coordination of developmental signaling is an important role for TAZ. In fact, TAZ is also implicated in signaling by transforming growth factor–β, and Hippo signaling augments signaling through the Notch pathway. Add to this the earlier work on the transcriptional roles of TAZ, and also its identification as a component of an E3 ubiquitin ligase complex that degrades a kidney ion channel, and you have one busy protein indeed.

X. Varelas, B. W. Miller, R. Sopko, S. Song, A. Gregorieff, F. A. Fellouse, R. Sakuma, T. Pawson, W. Hunziker, H. McNeill, J. L. Wrana, L. Attisano, The Hippo pathway regulates Wnt/β-catenin signaling. Dev. Cell 18, 579–591 (2010). [PubMed]

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