Abstract
The Hippo pathway is a critical transcriptional signaling pathway that regulates cell growth, proliferation and organ development. The transcriptional enhanced associate domain (TEAD) protein family consists of four paralogous transcription factors that function to modulate gene expression in response to the Hippo signaling pathway. Transcriptional activation of these proteins occurs upon binding to the co-activator YAP/TAZ whose entry into the nucleus is regulated by Lats1/2 kinase. In recent years, it has become apparent that the dysregulation and/or overexpression of Hippo pathway effectors is implicated in a wide range of cancers, including prostate, gastric and liver cancer. A large body of work has been dedicated to understanding the therapeutic potential of modulating the phosphorylation and localization of YAP/TAZ. However, YAP/TAZ are considered to be natively unfolded and may be intractable as drug targets. Therefore, TEAD proteins present themselves as an excellent therapeutic target for intervention of the Hippo pathway. This review summarizes the functional role of TEAD proteins in cancer and assesses the therapeutic potential of antagonizing TEAD function in vivo.
Highlights
Transcriptional enhanced associate domain (TEAD) transcription factors function in response to the highly conserved Hippo signaling pathway to regulate cell growth and proliferation.Transcriptional activation by TEAD requires complex formation with a transcription co-activator and TEAD’s cognate DNA sequence
We focus on recent progress that has been made towards understanding the function of the TEAD family of transcription factors and discuss their utility as an oncogenic target for therapeutic intervention
Function and inhibitory potential of TEAD has been aided by structure-based studies focused on and TAZ are composed of a transcriptional activation domain, which is partly composed of a either the DNA Binding Domain (DBD) or the YAP Binding Domain (YBD) of TEAD
Summary
Transcriptional enhanced associate domain (TEAD) transcription factors function in response to the highly conserved Hippo signaling pathway to regulate cell growth and proliferation. Inhibitory potential of TEAD has been aided by structure-based studies focused on either the DBD or deactivation of the Hippo pathway results in cell growth and tumors [19]. Lats1/2domain phosphorylation, which a TEAD phospho-binding on YAP/TAZ transcriptional activation (Figure 2). TAZ contain to activate gene [3], transcription, the molecular mechanism by which this transcriptional remains elusive2), atwhich this time due to the full-length TEAD structures either 1activation or 2 WWoccurs domains The C-terminal region of YAP function and inhibitory potential of TEAD has been aided by structure-based studies focused on and TAZ are composed of a transcriptional activation domain, which is partly composed of a either the DBD or the YBD of TEAD. Of the PDZ-binding motif significantly inhibited the oncogenic transformation of cultured cells when
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