TAZ: A novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins

Fumihiko Kanai, Paola A. Marignani, Dilara Sarbassova, Ryohei Yagi, Randy A. Hall, Mark Donowitz, Akihiko Hisaminato, Tsutomu Fujiwara, Yoshiaki Ito, Lewis C. Cantley, Michael B. Yaffe

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6778-6791
Number of pages14
JournalEMBO Journal
Volume19
Issue number24
DOIs
StatePublished - Dec 15 2000

Keywords

  • 14-3-3
  • Co-activator
  • PEBP2
  • PY motif
  • Runx

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Kanai, F., Marignani, P. A., Sarbassova, D., Yagi, R., Hall, R. A., Donowitz, M., Hisaminato, A., Fujiwara, T., Ito, Y., Cantley, L. C., & Yaffe, M. B. (2000). TAZ: A novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins. EMBO Journal, 19(24), 6778-6791. https://doi.org/10.1093/emboj/19.24.6778