Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28515457
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Crystal structure of TAZ-TEAD complex reveals a distinct interaction mode from
that of YAP-TEAD complex
#MMPMID28515457
Kaan HYK
; Chan SW
; Tan SKJ
; Guo F
; Lim CJ
; Hong W
; Song H
Sci Rep
2017[May]; 7
(1
): 2035
PMID28515457
show ga
The Hippo pathway is a tumor suppressor pathway that is implicated in the
regulation of organ size. The pathway has three components: the upstream
regulatory factors, the kinase core, and the downstream transcriptional
machinery, which consists of YAP, TAZ (transcription co-activators) and TEAD
(transcription factor). Formation of YAP/TAZ-TEAD complexes leads to the
transcription of growth-promoting genes. Herein, we report the crystal structure
of TAZ-TEAD4 complex, which reveals two binding modes. The first is similar to
the published YAP-TEAD structure. The second is a unique binding mode, whereby
two molecules of TAZ bind to and bridge two molecules of TEAD4. We validated the
latter using cross-linking and multi-angle light scattering. Using siRNA, we
showed that TAZ knockdown leads to a decrease in TEAD4 dimerization. Lastly,
results from luciferase assays, using YAP/TAZ transfected or knockdown cells,
give support to the non-redundancy of YAP/TAZ co-activators in regulating gene
expression in the Hippo pathway.
|*Models, Molecular
[MESH]
|*Protein Conformation
[MESH]
|Acyltransferases
[MESH]
|Adaptor Proteins, Signal Transducing/*chemistry/metabolism
[MESH]
free
free
free
