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 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.
Kanai
F
F
Division 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.
Marignani
P A
PA
Sarbassova
D
D
Yagi
R
R
Hall
R A
RA
Donowitz
M
M
Hisaminato
A
A
Fujiwara
T
T
Ito
Y
Y
Cantley
L C
LC
Yaffe
M B
MB
D048948:14-3-3 Proteins; D000217:Acyltransferases; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D002645:Chickens; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011506:Proteins; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D048948:14-3-3 Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D011506:Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D014446:Tyrosine 3-Monooxygenase; D000217:Acyltransferases; C486363:tafazzin protein, mouse; C108675:TAFAZZIN protein, human