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