Skip to main page content
U.S. flag
See More

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2012 Sep;23(7):785-93.
doi: 10.1016/j.semcdb.2012.05.004. Epub 2012 May 29.

The YAP and TAZ transcription co-activators: key downstream effectors of the mammalian Hippo pathway

Wanjin Hong  1 , Kun-Liang Guan
Affiliations
Review

The YAP and TAZ transcription co-activators: key downstream effectors of the mammalian Hippo pathway

Wanjin Hong et al. Semin Cell Dev Biol. 2012 Sep.

Abstract

The Hippo signaling pathway was initially defined by genetic studies in Drosophila to regulate tissue growth and organ size [1,2]. This pathway is highly conserved in mammals and dysregulation of the Hippo pathway has been implicated in human cancer. Although the exact extracellular signal that controls the Hippo pathway is currently unknown, compelling evidence supports a critical role of the Hippo pathway in cell contact inhibition, which is a property commonly lost in cancer cells. Many molecules, such as the merlin tumor suppressor protein, have been identified as regulating the activity of the core Hippo pathway components [1,2]. Acting downstream are two key transcription co-activators, YAP and TAZ, which mediate the major gene regulation and biological functions of the Hippo pathway. This article will focus on the physiological function and molecular regulation of YAP/TAZ and its Drosophila homolog Yki.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Domain organization of YAP, TAZ and Yki. A. The schematic drawing of YAP, TAZ and Yki. The key features are indicated such as the Pro-rich region, the WW domain, and coiled coil region. The HXRXXS motifs targeted by the Hippo pathway are also indicated with the major site in purple. The DSG-degron at the C-terminal part of YAP and TAZ is shown in blue, and the additional N-terminal DSGXXS degron of TAZ is also indicated. B. Alignment of the N-terminal region of YAP, TAZ and Yki. Residues identical in all three proteins are indicated in red with yellow background. The residues experimentally demonstrated to be involved in interaction with TEADs are indicated with purple ovals (using TAZ in the study) and arrow (using YAP in the analysis) below the alignment. These residues are located within the alpha1 and alpha2 helices (indicated above the alignment), which were revealed structurally to contact TEADs directly. The major Hippo target site whose phosphorylation created a binding site for 14–3–3 proteins is also highlighted.
Figure 2
Figure 2
Domain organization of TEADs and scalloped (Sd). The N-terminal region of TEADs and Sd contains the highly conserved TEA domain responsible for interaction with DNA elements such as GGAATG in the promoter region of target genes (such as CTGF and Axl). The amino acid alignment of the TEA domain of TEAD1–4 and Sd is also shown. The TEA domain forms a 3-helix bundle and the regions for the three helices are indicated on top. The nuclear localization signal is indicated below the alignment. The C-terminal region of TEADs and Sd is responsible for interaction with YAP/TAZ/Yki. Three residues conserved in TEADs and Sd that were experimentally demonstrated (using mouse TEAD4 in the study) to be important for interaction with YAP/TAZ/Yki (using mouse YAP as an interacting partner) are indicated (T1–T4 for TEAD1–4; T4m for mouse TEAD4, Sd for fly scalloped).
Figure 3
Figure 3
Summary of proteins shown to interact with YAP/TAZ/Yki. Amot family proteins are present only in mammalian cells but the drosophila expanded has been shown to interact with WW domain of fly Yki. The potential factors that interact with the C-terminal transactivation domain to promote transcriptional program are yet to be defined. The C-terminal PZD-binding motif is specific for YAP and TAZ but not present in Yki and has been shown to interact with ZO2 and NHERF2. Not all proteins interact with YAP at the same time. In fact, some interaction may be mutually exclusive. For example, the 14–3–3 associated YAP would be in cytoplasm whereas the TEAD associated YAP should be nuclear.
See this image and copyright information in PMC

References

    1. Zhao B, Li L, Lei Q, Guan KL. The Hippo-YAP pathway in organ size control and tumorigenesis: an updated version. Genes Dev. 2010;24:862–74. - PMC - PubMed
    1. Pan D. The hippo signaling pathway in development and cancer. DevCell. 2010;19:491–505. - PMC - PubMed
    1. Sudol M. Yes-associated protein (YAP65) is a proline-rich phosphoprotein that binds to the SH3 domain of the Yes proto-oncogene product. Oncogene. 1994;9:2145–52. - PubMed
    1. Sudol M, Bork P, Einbond A, Kastury K, Druck T, Negrini M, et al. Characterization of the mammalian YAP (Yes-associated protein) gene and its role in defining a novel protein module, the WW domain. J Biol Chem. 1995;270:14733–41. - PubMed
    1. Bork P, Sudol M. The WW domain: a signalling site in dystrophin? Trends Biochem Sci. 1994;19:531–3. - PubMed

Substances

LinkOut - more resources