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融合抑制基因参与果蝇中的刺猬信号转导,在哺乳动物中是保守的。

The Suppressor of fused gene, involved in Hedgehog signal transduction in Drosophila, is conserved in mammals.

作者信息

Delattre M, Briand S, Paces-Fessy M, Blanchet-Tournier M F

机构信息

Institut Jacques Monod, Laboratoire Génétique du Développement et Evolution, Universités Pierre et Marie Curie et Denis Diderot, 2 place Jussieu, F-75251 Paris cedex 05, France.

出版信息

Dev Genes Evol. 1999 May;209(5):294-300. doi: 10.1007/s004270050255.

DOI:10.1007/s004270050255
PMID:11252182
Abstract

The Suppressor of fused [Su(fu)] gene of Drosophila melanogaster encodes a protein containing a PEST sequence [sequence enriched in proline (P), glutamic acid (E), serine (S) and threonine (T)] which acts as an antagonist to the serine-threonine kinase Fused in Hedgehog (Hh) signal transduction during embryogenesis. The Su(fu) gene isolated from a distantly related Drosophila species, D. virilis, shows significantly high homology throughout its protein sequence with its D. melanogaster counterpart. We show that these two Drosophila homologs of Su(fu) are functionally interchangeable in enhancing the fused phenotype. We have also isolated mammalian homologs of Su(fu). The absence of the PEST sequence in the mammalian Su(fu) protein suggests a different regulation for this product between fly and vertebrates. Using the yeast two-hybrid method, we show that the murine Su(fu) protein can interact directly with the Fused and Cubitus interruptus proteins, known partners of Su(fu) in Drosophila. These data are discussed in the light of their evolutionary relationships.

摘要

黑腹果蝇的融合抑制基因[Su(fu)]编码一种含有PEST序列(富含脯氨酸(P)、谷氨酸(E)、丝氨酸(S)和苏氨酸(T)的序列)的蛋白质,该蛋白质在胚胎发育过程中作为刺猬信号通路(Hh)中丝氨酸-苏氨酸激酶Fused的拮抗剂发挥作用。从远缘果蝇物种果蝇中分离出的Su(fu)基因,在其整个蛋白质序列中与其黑腹果蝇对应物具有显著的高度同源性。我们发现,Su(fu)的这两个果蝇同源物在增强融合表型方面功能上是可互换的。我们还分离出了Su(fu)的哺乳动物同源物。哺乳动物Su(fu)蛋白中不存在PEST序列,这表明该产物在果蝇和脊椎动物之间存在不同的调控方式。利用酵母双杂交方法,我们发现小鼠Su(fu)蛋白可以直接与Fused和Cubitus interruptus蛋白相互作用,这两种蛋白是果蝇中已知的Su(fu)的相互作用伴侣。我们根据它们的进化关系对这些数据进行了讨论。

相似文献

1
The Suppressor of fused gene, involved in Hedgehog signal transduction in Drosophila, is conserved in mammals.融合抑制基因参与果蝇中的刺猬信号转导,在哺乳动物中是保守的。
Dev Genes Evol. 1999 May;209(5):294-300. doi: 10.1007/s004270050255.
2
Suppressor of fused links fused and Cubitus interruptus on the hedgehog signalling pathway.融合抑制因子在刺猬信号通路中连接融合蛋白和截翅蛋白。
Curr Biol. 1998 May 7;8(10):583-6. doi: 10.1016/s0960-9822(98)70227-1.
3
Vertebrate homologs of Drosophila suppressor of fused interact with the gli family of transcriptional regulators.果蝇融合抑制因子的脊椎动物同源物与转录调节因子Gli家族相互作用。
Dev Biol. 1999 Aug 15;212(2):323-36. doi: 10.1006/dbio.1999.9335.
4
Modulation of the Suppressor of fused protein regulates the Hedgehog signaling pathway in Drosophila embryo and imaginal discs.融合蛋白抑制因子的调控作用调节果蝇胚胎和成虫盘的Hedgehog信号通路。
Dev Biol. 2006 Mar 1;291(1):53-66. doi: 10.1016/j.ydbio.2005.12.004. Epub 2006 Jan 18.
5
Divergence of hedgehog signal transduction mechanism between Drosophila and mammals.果蝇与哺乳动物之间刺猬信号转导机制的差异。
Dev Cell. 2006 Feb;10(2):177-86. doi: 10.1016/j.devcel.2005.12.014.
6
Modulation of Hedgehog target gene expression by the Fused serine-threonine kinase in wing imaginal discs.翅成虫盘内融合丝氨酸 - 苏氨酸激酶对刺猬信号通路靶基因表达的调控
Mech Dev. 1998 Nov;78(1-2):17-31. doi: 10.1016/s0925-4773(98)00130-0.
7
Characterization of the human suppressor of fused, a negative regulator of the zinc-finger transcription factor Gli.锌指转录因子Gli的负调控因子——人融合抑制因子的特性分析
J Cell Sci. 1999 Dec;112 ( Pt 23):4437-48. doi: 10.1242/jcs.112.23.4437.
8
Genetic dissection of the Drosophila Cubitus interruptus signaling complex.果蝇翅脉中断信号复合体的遗传学剖析
Dev Biol. 2001 Aug 15;236(2):411-20. doi: 10.1006/dbio.2001.0345.
9
Hedgehog stimulates maturation of Cubitus interruptus into a labile transcriptional activator.刺猬索尼克信号通路刺激间断翅脉蛋白成熟为一种不稳定的转录激活因子。
Nature. 1998;396(6713):749-53. doi: 10.1038/25533.
10
Suppressor of fused opposes hedgehog signal transduction by impeding nuclear accumulation of the activator form of Cubitus interruptus.融合抑制因子通过阻止间断翅脉激活形式的核积累来对抗刺猬信号转导。
Development. 2000 Sep;127(18):4001-10. doi: 10.1242/dev.127.18.4001.

引用本文的文献

1
Molecular mechanisms of suppressor of fused in regulating the hedgehog signalling pathway.融合抑制因子调控刺猬信号通路的分子机制
Oncol Lett. 2018 May;15(5):6077-6086. doi: 10.3892/ol.2018.8142. Epub 2018 Mar 1.
2
Biophysical characterisation of the novel zinc binding property in Suppressor of Fused.新型锌结合特性在融合抑制因子中的生物物理特性分析。
Sci Rep. 2017 Sep 11;7(1):11139. doi: 10.1038/s41598-017-11203-2.
3
Basic biology and mechanisms of neural ciliogenesis and the B9 family.神经纤毛发生的基础生物学和机制及 B9 家族。
Mol Neurobiol. 2012 Jun;45(3):564-70. doi: 10.1007/s12035-012-8276-7. Epub 2012 May 30.
4
Loss of the serine/threonine kinase fused results in postnatal growth defects and lethality due to progressive hydrocephalus.丝氨酸/苏氨酸激酶fused的缺失会导致出生后生长缺陷,并因进行性脑积水而致死。
Mol Cell Biol. 2005 Aug;25(16):7054-68. doi: 10.1128/MCB.25.16.7054-7068.2005.
5
Mice deficient in the fused homolog do not exhibit phenotypes indicative of perturbed hedgehog signaling during embryonic development.缺乏融合同源物的小鼠在胚胎发育过程中未表现出刺猬信号通路紊乱的表型。
Mol Cell Biol. 2005 Aug;25(16):7042-53. doi: 10.1128/MCB.25.16.7042-7053.2005.
6
Suppressor of fused regulates Gli activity through a dual binding mechanism.融合抑制因子通过双重结合机制调节Gli活性。
Mol Cell Biol. 2004 Oct;24(19):8627-41. doi: 10.1128/MCB.24.19.8627-8641.2004.
7
The negative regulator of Gli, Suppressor of fused (Sufu), interacts with SAP18, Galectin3 and other nuclear proteins.Gli的负调节因子,融合抑制因子(Sufu),与SAP18、半乳糖凝集素3及其他核蛋白相互作用。
Biochem J. 2004 Mar 1;378(Pt 2):353-62. doi: 10.1042/BJ20030786.