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| The EMBO Journal
(2000) 19, 6778–6791, doi:10.1093/emboj/19.24.6778 |
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| TAZ: a novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins |
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| Fumihiko Kanai1, 2, Paola A. Marignani1, Dilara Sarbassova1, Ryohei Yagi3, 4, Randy A. Hall5, Mark Donowitz6, Akihiko Hisaminato7, Tsutomu Fujiwara7, Yoshiaki Ito3, Lewis C. Cantley1, 2 and Michael B. Yaffe1, 8 |
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1 Division of Signal Transduction, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA 2 Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA 3 Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto 606-8507 Japan 4 Present address: Department of Molecular Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan 5 Department of Pharmacology, Rollins Research Center, Emory University School of Medicine, Atlanta, GA 30322, USA 6 Department of Medicine, GI Division, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA 7 Otsuka GEN Research Institute, Otsuka Pharmaceutical Co. Ltd, Tokushima 771-0192, Japan 8 Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA To whom correspondence should be addressed Michael B. Yaffe, myaffe@mit.edu Received 31 July 2000; Revised 18 October 2000; Accepted 18 October 2000. |
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| Abstract |
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| The highly conserved and ubiquitously expressed 14-3-3 proteins regulate differentiation, cell cycle progression and apoptosis by binding intracellular phosphoproteins involved in signal transduction. By screening in vitro translated cDNA pools for the ability to bind 14-3-3, we identified a novel transcriptional co-activator, TAZ (transcriptional co-activator with PDZ-binding motif) as a 14-3-3-binding molecule. TAZ shares homology with Yes-associated protein (YAP), contains a WW domain and functions as a transcriptional co-activator by binding to the PPXY motif present on transcription factors. 14-3-3 binding requires TAZ phosphorylation on a single serine residue, resulting in the inhibition of TAZ transcriptional co-activation through 14-3-3-mediated nuclear export. The C-terminus of TAZ contains a highly conserved PDZ-binding motif that localizes TAZ into discrete nuclear foci and is essential for TAZ-stimulated gene transcription. TAZ uses this same motif to bind the PDZ domain-containing protein NHERF-2, a molecule that tethers plasma membrane ion channels and receptors to cytoskeletal actin. TAZ may link events at the plasma membrane and cytoskeleton to nuclear transcription in a manner that can be regulated by 14-3-3. |
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| Keywords: 14-3-3, co-activator, PEBP2, PY motif, Runx |
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