MIM/BEG4, a Sonic hedgehog-responsive gene that potentiates Gli-dependent transcription

Genes Dev. 2004 Nov 15;18(22):2724-9. doi: 10.1101/gad.1221804.

Abstract

Sonic hedgehog (Shh) signaling plays a critical role during development and carcinogenesis. While Gli family members govern the transcriptional output of Shh signaling, little is known how Gli-mediated transcriptional activity is regulated. Here we identify the actin-binding protein Missing in Metastasis (MIM) as a new Shh-responsive gene. Together, Gli1 and MIM recapitulate Shh-mediated epidermal proliferation and invasion in regenerated human skin. MIM is part of a Gli/Suppressor of Fused complex and potentiates Gli-dependent transcription using domains distinct from those used for monomeric actin binding. These data define MIM as both a Shh-responsive gene and a new member of the pathway that modulates Gli responses during growth and tumorigenesis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism
  • Animals
  • Cell Division
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism
  • Epidermal Cells
  • Epidermis / metabolism
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Gene Expression Profiling
  • Hedgehog Proteins
  • Humans
  • Immunoprecipitation
  • In Situ Hybridization
  • Kruppel-Like Transcription Factors
  • Mice
  • Mice, Knockout
  • Microfilament Proteins / genetics
  • Microfilament Proteins / immunology
  • Microfilament Proteins / pharmacology*
  • Neoplasm Invasiveness / pathology*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology
  • Neoplasm Proteins / pharmacology*
  • Nuclear Proteins
  • Oligonucleotide Array Sequence Analysis
  • Protein Binding
  • Protein Structure, Tertiary
  • Rabbits
  • Recombinant Fusion Proteins / metabolism
  • Regeneration
  • Repressor Proteins / metabolism
  • Skin / cytology*
  • Skin / metabolism
  • Trans-Activators / metabolism
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic*
  • Zinc Finger Protein GLI1
  • Zinc Finger Protein Gli2
  • Zinc Fingers

Substances

  • Actins
  • GLI1 protein, human
  • GLI2 protein, human
  • Gli1 protein, mouse
  • Gli2 protein, mouse
  • Hedgehog Proteins
  • Kruppel-Like Transcription Factors
  • Microfilament Proteins
  • Mtss1 protein, mouse
  • Neoplasm Proteins
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • SHH protein, human
  • Sufu protein, mouse
  • Trans-Activators
  • Transcription Factors
  • Zinc Finger Protein GLI1
  • Zinc Finger Protein Gli2