Mammalian suppressor-of-fused modulates nuclear-cytoplasmic shuttling of Gli-1
| Autor: | Rune Toftgård, Peter G. Zaphiropoulos, Thomas Grimm, Lembi Kogerman, Darren Krause, Anne Birgitte Undén, Priit Kogerman, Bengt Sandstedt |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Patched
Adult Cytoplasm animal structures Embryo Nonmammalian Transcription Genetic Cellular differentiation Molecular Sequence Data Transfection Zinc Finger Protein GLI1 Cell Line Mice Osteogenesis Animals Drosophila Proteins Humans Amino Acid Sequence Sonic hedgehog Nuclear export signal Regulation of gene expression Cell Nucleus Mammals Oncogene Proteins Osteoblasts integumentary system biology Sequence Homology Amino Acid Effector Gene Expression Regulation Developmental Cell Differentiation Cell Biology Embryo Mammalian Hedgehog signaling pathway Recombinant Proteins Cell biology Repressor Proteins Drosophila melanogaster embryonic structures biology.protein Trans-Activators Chickens Sequence Alignment Transcription Factors |
| Zdroj: | Nature cell biology. 1(5) |
| ISSN: | 1465-7392 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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