Pham A, Therond P, Alves G, Tournier F B, Busson D, Lamour-Isnard C, Bouchon B L, Préat T, Tricoire H
Laboratoire de Génétique du Développement et Evolution, Institut Jaques Monod, Paris, France.
Genetics. 1995 Jun;140(2):587-98. doi: 10.1093/genetics/140.2.587.
Suppressor of fused, Su(fu), was identified as a semi-dominant suppressor of the putative serine/threonine kinase encoded by the segment polarity gene fused in Drosophila melanogaster. The amorphic Su(fu) mutation is viable, shows a maternal effect and displays no phenotype by itself. Su(fu) mutations are often found associated to karmoisin (kar) mutations but two complementation groups can be clearly identified. By using a differential hybridization screening method, we have cloned the Su(fu) region and identified chromosomal rearrangements associated with Su(fu) mutations. Two classes of cDNAs with similar developmental patterns, including a maternal contribution, are detectable in the region. Transformation experiments clearly assigned the Su(fu)+ function to one of these transcription units while the other one can be most likely assigned to the kar+ function. Surprisingly the 5' end of the kar RNA mapped within the 3' untranslated region of the Su(fu) transcribed sequence. The Su(fu) gene encodes a 53-kD protein, which contains a PEST sequence and shows no significant homologies with known proteins. Genetic analysis shows that proper development requires a fine tuning of the genetic doses of fu and Su(fu) both maternally and zygotically. These results, together with previous genetic and molecular data, suggest that fused and Suppressor of fused could act through a competitive posttraductionnal modification of a common target in the hedgehog signaling pathway.
融合抑制因子(Su(fu))最初被鉴定为果蝇中由节段极性基因融合所编码的假定丝氨酸/苏氨酸激酶的半显性抑制因子。无义突变的Su(fu)是可存活的,表现出母体效应,且自身无表型。Su(fu)突变常与卡莫辛(kar)突变相关,但可明确鉴定出两个互补群。通过差异杂交筛选方法,我们克隆了Su(fu)区域并鉴定了与Su(fu)突变相关的染色体重排。在该区域可检测到两类具有相似发育模式(包括母体贡献)的cDNA。转化实验明确将Su(fu)+功能赋予其中一个转录单位,而另一个很可能赋予kar+功能。令人惊讶的是,kar RNA的5'端定位于Su(fu)转录序列的3'非翻译区内。Su(fu)基因编码一种53-kD的蛋白质,该蛋白质含有一个PEST序列,与已知蛋白质无明显同源性。遗传分析表明,正常发育需要在母体和合子中对fu和Su(fu)的基因剂量进行精细调节。这些结果与先前的遗传和分子数据一起表明,融合基因和融合抑制因子可能通过对刺猬信号通路中一个共同靶点进行竞争性的翻译后修饰来发挥作用。