ROLE OF UBIQUITIM-LIKE PROTEINS IN DICTYOSTELIU

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.