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

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.
Mesh Terms:
Adult, Amino Acid Sequence, Animals, Cell Differentiation, Cell Line, Cell Nucleus, Chickens, Cytoplasm, Drosophila Proteins, Drosophila melanogaster, Embryo, Mammalian, Embryo, Nonmammalian, Gene Expression Regulation, Developmental, Humans, Mammals, Mice, Molecular Sequence Data, Oncogene Proteins, Osteoblasts, Osteogenesis, Recombinant Proteins, Repressor Proteins, Sequence Alignment, Sequence Homology, Amino Acid, Trans-Activators, Transcription Factors, Transcription, Genetic, Transfection
Nat. Cell Biol.
Date: Sep. 01, 1999
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