ROLE OF UBIQUITIM-LIKE PROTEINS IN DICTYOSTELIU

NOSA编码泛素化系统的一种新成分。之后 基因的克隆和鉴定，我们发现基因的破坏 在细胞形成之前改变泛素化并阻止发育 孢子。NOSA的C-末端区域与S. Cerevisiae，一种参与泛素介导的细胞降解的蛋白质 特定的人造底物。Ufd2p没有已知的内源底物 UFD2突变体没有表现出改变的表型。也有基因 在线虫和人类中与NOSA同源，由此我们推断 该基因的功能是保守的。 我们利用了NOSA突变体无法形成 孢子。17个携带抑制该效应的突变的菌株 已经被分离出来了。第一个等位基因 被定性的被称为索纳。索纳由一种类似泛素的 结构域(而不是泛素本身)和长的C-末端延伸。 我们认为NOSA参与了泛素化和随后的 降解索纳，也许还有其他泛素样蛋白。在S。 Cerevisiae，一种名为DSK2的基因与SONA同源。Dsk2p是 牵涉到纺锤体极体的形成。在人类中，泛素样蛋白 在许多蛋白质中发现了结构域，突变会引起这些结构域的变化 青少年帕金森氏症、着色性干皮病和早幼粒细胞增多症 白血病。 NOSA突变体中影响的生物学过程的线索 Dictyostelials是由SonB提供的，SonB编码CDK7，这是一种激酶亚单位 Cdc2激活激酶，这对G2到M至关重要 在细胞周期中的过渡。NOSA效应的一种解释 突变是NOSA和SONA是机制的一部分 Dictyostoma阿米巴用于阻止它们的细胞周期或感觉 当他们进入发育阶段时，他们会挨饿。

NosA codes for a novel component of the ubiquitination system. After cloning and characterization of the gene, we showed that gene disruption alters ubiquitination and blocks development before the cells make spores. The C-terminal region of NosA is homologous to Ufd2p of S. cerevisiae, a protein involved in ubiquitin-mediated degradation of specific artificial substrates. Ufd2p has no known endogenous substrates and UFD2 mutants present no altered phenotype. There are also genes homologous to nosA in C. elegans and in humans, from which we infer that the function of this gene is conserved. We have taken advantage of the inability of the nosA mutant to form spores. Seventeen strains carrying mutations that suppress the effect of nosA on development have been isolated. The first of these alleles to be characterized is called sonA. SonA consists of a ubiquitin-like domain (rather than ubiquitin itself) and a long C-terminal extension. We propose that NosA participates in the ubiquitination and subsequent degradation of SonA and perhaps other ubiquitin-like proteins. In S. cerevisiae, a gene called DSK2 is homologous to sonA. Dsk2p is implicated in spindle pole body formation. In humans, ubiquitin-like domains are found in a number of proteins in which mutation gives rise to juvenile Parkinsonism, xeroderma pigmentosum, and promyelocytic leukemia. A clue to the biological process that is affected in nosA mutants of Dictyostelium is given by SonB, which codes for Cdk7, the kinase subunit of the cdc2-activating kinase, which is crucial to the G2 to M transition during the cell cycle. One explanation for the effect of nosA mutation is that NosA and SonA are part of the mechanism which Dictyostelium amoebae use to arrest their cell cycles or sense starvation when they enter development.