Mammalian suppressor-of-fused modulates nuclear-cytoplasmic shuttling of Gli-1

Nat Cell Biol. 1999 Sep;1(5):312-9. doi: 10.1038/13031.


Sonic hedgehog, Patched and Gli are components of a mammalian signalling pathway that has been conserved during evolution and which has a central role in the control of pattern formation and cellular proliferation during development. Here we identify the human Suppressor-of-Fused (SUFUH) complementary DNA and show that the gene product interacts physically with the transcriptional effector GLI-1, can sequester GLI-1 in the cytoplasm, but can also interact with GLI-1 on DNA. Functionally, SUFUH inhibits transcriptional activation by GLI-1, as well as osteogenic differentiation in response to signalling from Sonic hedgehog. Localization of GLI-1 is influenced by the presence of a nuclear-export signal, and GLI-1 becomes constitutively nuclear when this signal is mutated or nuclear export is inhibited. These results show that SUFUH is a conserved negative regulator of GLI-1 signalling that may affect nuclear-cytoplasmic shuttling of GLI-1 or the activity of GLI-1 in the nucleus and thereby modulate cellular responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Animals
  • Cell Differentiation
  • Cell Line
  • Cell Nucleus / metabolism*
  • Chickens
  • Cytoplasm / metabolism
  • Drosophila Proteins*
  • Drosophila melanogaster / genetics
  • Embryo, Mammalian
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental
  • Humans
  • Mammals
  • Mice
  • Molecular Sequence Data
  • Oncogene Proteins / metabolism*
  • Osteoblasts / metabolism
  • Osteogenesis
  • Recombinant Proteins / metabolism
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Trans-Activators
  • Transcription Factors / metabolism*
  • Transcription, Genetic*
  • Transfection
  • Zinc Finger Protein GLI1


  • Drosophila Proteins
  • Oncogene Proteins
  • Recombinant Proteins
  • Repressor Proteins
  • SUFU protein, human
  • Su(fu) protein, Drosophila
  • Sufu protein, mouse
  • Trans-Activators
  • Transcription Factors
  • Zinc Finger Protein GLI1

Associated data

  • GENBANK/AF175770