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The Hippo Pathway and YAP/TAZ–TEAD Protein–Protein Interaction as Targets for Regenerative Medicine and Cancer Treatment

Authors :
Maria Paola Costi
Stefania Ferrari
Tatiana Vignudelli
Matteo Santucci
Elisa Uliassi
Marco Mor
Laura Scalvini
Maria Laura Bolognesi
Source :
Journal of Medicinal Chemistry. 58:4857-4873
Publication Year :
2015
Publisher :
American Chemical Society (ACS), 2015.

Abstract

The Hippo pathway is an important organ size control signaling network and the major regulatory mechanism of cell-contact inhibition. Yes associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are its targets and terminal effectors: inhibition of the pathway promotes YAP/TAZ translocation to the nucleus, where they interact with transcriptional enhancer associate domain (TEAD) transcription factors and coactivate the expression of target genes, promoting cell proliferation. Defects in the pathway can result in overgrowth phenotypes due to deregulation of stem-cell proliferation and apoptosis; members of the pathway are directly involved in cancer development. The pharmacological regulation of the pathway might be useful in cancer prevention, treatment, and regenerative medicine applications; currently, a few compounds can selectively modulate the pathway. In this review, we present an overview of the Hippo pathway, the sequence and structural analysis of YAP/TAZ, the known ...

Details

ISSN :
15204804 and 00222623
Volume :
58
Database :
OpenAIRE
Journal :
Journal of Medicinal Chemistry
Accession number :
edsair.doi...........be16acf37394838270864edec73ed411
Full Text :
https://doi.org/10.1021/jm501615v