Crystal structure of TAZ-TEAD complex reveals a distinct interaction mode from that of YAP-TEAD complex

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 (tra...

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Veröffentlicht in:Scientific reports 2017-05, Vol.7 (1), p.2035-11, Article 2035
Hauptverfasser: Kaan, Hung Yi Kristal, Chan, Siew Wee, Tan, Siew Kim Joyce, Guo, Fusheng, Lim, Chun Jye, Hong, Wanjin, Song, Haiwei
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Sprache:eng
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Zusammenfassung: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-02219-9