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

The highly conserved and ubiquitously expressed 14-3-3 proteins regulate di fferentiation, cell cycle progression and apoptosis by binding intracellula r phosphoproteins involved in signal transduction. By screening in vitro tr anslated cDNA pools for the ability to bind 14-3-3, we identified a novel t ranscriptional co-activator, TAZ (transcriptional co-activator with PDZ-bin ding motif) as a 14-3-3-binding molecule. TAZ shares homology with Yes-asso ciated protein (YAP), contains a WW domain and functions as a transcription al co-activator by binding to the PPXY motif present on transcription facto rs. 14-3-3 binding requires TAZ phosphorylation on a single serine residue, resulting in the inhibition of TAZ transcriptional co-activation through 1 4-3-3-mediated nuclear export. The C-terminus of TAZ contains a highly cons erved PDZ-binding motif that localizes TAZ into discrete nuclear foci and i s 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 transcriptio n in a manner that can be regulated by 14-3-3.