Kogerman P, Grimm T, Kogerman L, Krause D, Undén A B, Sandstedt B, Toftgård R, Zaphiropoulos P G
Karolinska Institutet, Department of Biosciences, Huddinge, Sweden.
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.
音猬因子、 patched 蛋白和 Gli 蛋白是一种哺乳动物信号通路的组成部分，该信号通路在进化过程中得以保留，并且在发育过程中对模式形成和细胞增殖的控制起着核心作用。在此，我们鉴定出了人类融合抑制因子（SUFUH）的互补 DNA，并表明该基因产物与转录效应因子 GLI-1 存在物理相互作用，能够将 GLI-1 隔离在细胞质中，但也能在 DNA 上与 GLI-1 相互作用。在功能上，SUFUH 抑制 GLI-1 的转录激活，以及对音猬因子信号作出反应的成骨分化。GLI-1 的定位受核输出信号的影响，当该信号发生突变或核输出受到抑制时，GLI-1 会持续定位于细胞核。这些结果表明，SUFUH 是 GLI-1 信号通路中保守的负调节因子，可能影响 GLI-1 在细胞核与细胞质之间的穿梭，或影响 GLI-1 在细胞核中的活性，从而调节细胞反应。
