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

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          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 pharmacological modulators of the pathway, especially those targeting YAP/TAZ-TEAD interaction.

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          Author and article information

          Journal
          J. Med. Chem.
          Journal of medicinal chemistry
          American Chemical Society (ACS)
          1520-4804
          0022-2623
          Jun 25 2015
          : 58
          : 12
          Affiliations
          [1 ] †Department of Life Sciences, University of Modena and Reggio Emilia, Via Giuseppe Campi 183, Modena 41125, Italy.
          [2 ] ‡Department of Pharmacy, University of Parma, Parco Area delle Scienze 27/A, Parma 43124, Italy.
          [3 ] §Department of Pharmacy and Biotechnology, University of Bologna, Via Belmeloro 6, Bologna 40126, Italy.
          Article
          10.1021/jm501615v
          25719868
          9f5188e9-f603-4e23-8e3c-f3fc4b9cbc8a
          History

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