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TAZ: a novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins
F Kanai1, P A Marignani, D Sarbassova
1Division of Signal Transduction, Department of Medicine and Department of Surgery, Beth Israel Deaconess Medical Center, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
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.
Insights
Researchers discovered a new transcriptional co-activator, TAZ, that binds to 14-3-3 proteins. This interaction regulates gene transcription by controlling TAZ
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- 14-3-3 proteins are crucial regulators of cellular processes.
- They bind phosphoproteins involved in signal transduction.
Purpose of the Study:
- Identify novel 14-3-3 binding molecules.
- Characterize the function of the identified transcriptional co-activator, TAZ.
Main Methods:
- In vitro translation and cDNA pool screening.
- Analysis of protein-protein interactions and subcellular localization.
- Assays for transcriptional co-activation.
Main Results:
- TAZ (transcriptional co-activator with PDZ-binding motif) was identified as a 14-3-3 binding protein.
- 14-3-3 binding, mediated by TAZ phosphorylation, inhibits TAZ activity via nuclear export.
- TAZ's PDZ-binding motif is essential for nuclear localization and transcriptional activity, and mediates interaction with NHERF-2.
Conclusions:
- TAZ functions as a transcriptional co-activator regulated by 14-3-3 proteins.
- TAZ links extracellular signals and cytoskeletal organization to nuclear gene transcription.