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 language | English (US) |
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Pages (from-to) | 6778-6791 |
Number of pages | 14 |
Journal | EMBO Journal |
Volume | 19 |
Issue number | 24 |
DOIs | |
State | Published - Dec 15 2000 |
Externally published | Yes |
Keywords
- 14-3-3
- Co-activator
- PEBP2
- PY motif
- Runx
ASJC Scopus subject areas
- General Neuroscience
- Molecular Biology
- General Biochemistry, Genetics and Molecular Biology
- General Immunology and Microbiology