Structural and functional similarity between the Vgll1-TEAD and the YAP-TEAD complexes

Structure. 2012 Jul 3;20(7):1135-40. doi: 10.1016/j.str.2012.04.004. Epub 2012 May 24.

Abstract

The structure of the complex between the transcription cofactor Vgll1 and the transcription factor TEAD4, the mammalian equivalent of the Drosophila Vestigial and Scalloped, respectively, is determined in this study. Remarkably, Vgll1 interacts with TEAD in a manner similar to the transcription coactivators, as well as oncogenes YAP and TAZ, despite having a varied primary sequence. Vgll1-TEAD complex upregulates the expression of IGFBP-5, a proliferation-promoting gene, and facilitates anchorage-independent cell proliferation. The YAP/TAZ-TEAD complex also upregulates several other proliferation-promoting genes and also promotes anchorage-independent cell proliferation. Given its structural and functional similarity to YAP/TAZ, Vgll1 has the potential to promote cancer progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Proliferation
  • Crystallography, X-Ray
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins / chemistry*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Humans
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Muscle Proteins / chemistry*
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Protein Binding
  • Protein Structure, Secondary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Signal Transduction
  • Structural Homology, Protein
  • Trans-Activators / chemistry*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / chemistry*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptional Activation

Substances

  • DNA-Binding Proteins
  • Dis3 protein, Drosophila
  • Drosophila Proteins
  • Muscle Proteins
  • Nuclear Proteins
  • Recombinant Proteins
  • Tead4 protein, mouse
  • Trans-Activators
  • Transcription Factors
  • VGLL1 protein, human
  • Yki protein, Drosophila

Associated data

  • PDB/4EAZ