Mammalian Suppressor-of-Fused modulates nuclear–cytoplasmic shuttling of GLI-1
Author: ["Priit Kogerman","Thomas Grimm","Lembi Kogerman","Darren Krause","Anne Birgitte Undén","Bengt Sandstedt","Rune Toftgård","Peter G. Zaphiropoulos"]
Publication: Nature Cell Biology
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Abstract
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.
Cite this article
Kogerman, P., Grimm, T., Kogerman, L. et al. Mammalian Suppressor-of-Fused modulates nuclear–cytoplasmic shuttling of GLI-1. Nat Cell Biol 1, 312–319 (1999). https://doi.org/10.1038/13031
