Temporal and spatial expression of the cell-cycle regulator cul-1 in Drosophila and its stimulation by radiation-induced apoptosis.

Cul-1 protein is part of the ubiquitin ligase complex that is conserved from yeast to humans. This complex specifically marks cell-cycle regulators for their subsequent destruction. Two null mutations of the cul-1 gene are known, in budding yeast and in nematodes. Although in both these organisms the cul-1 gene executes essentially the same function, the manifestation of its lack-of-function mutations differs considerably. In yeast the mutation causes arrest at the G(1)/S-phase transition, whereas in nematodes excessive cell divisions occur because mutant cells are unable to exit the mitotic cycle. We isolated cul-1 orthologues from two model organisms, Drosophila melanogaster and mouse. We show that the Drosophila full-length cul-1 gene restores the yeast mutant's inability to pass through the G(1)/S-phase transition. We also characterize expression of this gene at the transcript and protein levels during Drosophila development and show that cul-1 gene is maternally supplied as a protein, but not as an RNA transcript. Zygotic transcription of the gene, however, resumes at early stages of embryogenesis. We also found an increase in cul-1 transcription in cultured cells treated with a lethal dose of gamma-irradiation.