Characterization of Hippo Pathway Components by Gene Inactivation

Mol Cell. 2016 Dec 1;64(5):993-1008. doi: 10.1016/j.molcel.2016.10.034.

Abstract

The Hippo pathway is important for regulating tissue homeostasis, and its dysregulation has been implicated in human cancer. However, it is not well understood how the Hippo pathway becomes dysregulated because few mutations in core Hippo pathway components have been identified. Therefore, much work in the Hippo field has focused on identifying upstream regulators, and a complex Hippo interactome has been identified. Nevertheless, it is not always clear which components are the most physiologically relevant in regulating YAP/TAZ. To provide an overview of important Hippo pathway components, we created knockout cell lines for many of these components and compared their relative contributions to YAP/TAZ regulation in response to a wide range of physiological signals. By this approach, we provide an overview of the functional importance of many Hippo pathway components and demonstrate NF2 and RHOA as important regulators of YAP/TAZ and TAOK1/3 as direct kinases for LATS1/2.

Keywords: CRISPR; Hippo pathway; NF2; RHOA; TAOK1; TAOK3; TAZ; YAP.

MeSH terms

  • Cell Cycle Proteins
  • Clustered Regularly Interspaced Short Palindromic Repeats
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation / physiology*
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Neurofibromin 2
  • Nuclear Proteins
  • Phosphorylation
  • Protein-Serine-Threonine Kinases
  • Signal Transduction / genetics*
  • Transcription Factors
  • Tumor Suppressor Proteins
  • rhoA GTP-Binding Protein

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Neurofibromin 2
  • Nuclear Proteins
  • Transcription Factors
  • Tumor Suppressor Proteins
  • YY1AP1 protein, human
  • TAFAZZIN protein, human
  • LATS1 protein, human
  • LATS2 protein, human
  • Hippo protein, human
  • Protein-Serine-Threonine Kinases
  • TAO1 protein kinase
  • rhoA GTP-Binding Protein