Angiomotin'g YAP into the nucleus for cell proliferation and cancer development

Sci Signal. 2013 Sep 3;6(291):pe27. doi: 10.1126/scisignal.2004573.

Abstract

The Hippo pathway regulates cell proliferation and apoptosis during development, tissue regeneration, and carcinogenesis. Nuclear translocation of the transcription factors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) and their subsequent interaction with TEA domain (TEAD) transcriptional factors program pro-proliferative and antiapoptotic transcription. Scaffold proteins angiomotin (Amot) and angiomotin-related AmotL1 and AmotL2 were recently identified as negative regulators of YAP and TAZ by preventing their nuclear translocation. In this issue of Science Signaling, Yi et al. show that Amot may also promote nuclear translocation of YAP and act as a transcriptional cofactor of the YAP-TEAD complex to facilitate proliferation of biliary epithelial cells and cancer development of the liver either in response to tissue injury or in the absence of the tumor suppressor Merlin. These seemingly controversial results highlight that our understanding of Amot proteins in the Hippo pathway is so far limited.

Publication types

  • Review

MeSH terms

  • Active Transport, Cell Nucleus / genetics
  • Acyltransferases
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Motifs
  • Angiomotins
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Cell Nucleus / pathology
  • Cell Proliferation
  • Hippo Signaling Pathway
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microfilament Proteins
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Structure, Tertiary
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • YAP-Signaling Proteins

Substances

  • AMOT protein, human
  • AMOTL1 protein, human
  • AMOTL2 protein, human
  • Adaptor Proteins, Signal Transducing
  • Angiomotins
  • Carrier Proteins
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Microfilament Proteins
  • Phosphoproteins
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • Acyltransferases
  • TAFAZZIN protein, human
  • Protein Serine-Threonine Kinases