THE OVERGROWN HEMATOPOIETIC ORGANS-31 TUMOR-SUPPRESSOR GENE OF DROSOPHILA ENCODES AN IMPORTIN-LIKE PROTEIN ACCUMULATING IN THE NUCLEUS AT THE ONSET OF MITOSIS

The tumor suppressor gene overgrown hematopoietic organs-31 (oho31) of Drosophila encodes a protein with extensive homology to the Importin protein of Xenopus (50% identity), the related yeast SRP1 protein, and the mammalian hSRP1 and RCH1 proteins. A strong reduction in the expr ession of oho31 by a P element inserted in the 5' untranslated region of the oho31 transcript or a complete inactivation of oho31 by impreci se P element excision leads to malignant development of the hematopoie tic organs and the genital disc, as shown by their growth autonomy in transplantation assays. We have cloned the oho31 gene of Drosophila me lanogaster and determined its nucleotide sequence. The gene encodes a phosphoprotein of 522 amino acids made of three domains: a central hyd rophobic domain of eight repeats of 42-44 amino acids each, displaying similarity to the arm motif found in junctional and nucleopore comple x proteins, and flanked by two hydrophilic NH2- and COOH-terminal doma ins. Immunostaining revealed that the OHO31 protein is supplied matern ally and rapidly degraded during the first 13 nuclear divisions. There after, the OHO31 protein is predominantly expressed, albeit at reduced levels, in proliferating tissues. During the interphase of early embr yonic cell cycles, the OHO31 protein is present in the cytoplasm and m assively accumulates in the nucleus at the onset of mitosis in late in terphase and prophase. The nuclear import of OHO31 is, however, less p ronounced during later developmental stages. These results suggest tha t, similar to Importin, OHO31 may act as a cytosolic factor in nuclear transport. Moreover, the cell cycle-dependent accumulation of OHO31 i n the nucleus indicates that this protein may be required for critical nuclear reactions occurring at the onset of mitosis.