The overgrown hematopoietic organs-31 tumor suppressor gene of Drosophila encodes an Importin-like protein accumulating in the nucleus at the onset of mitosis.

Abstract

Abstract. 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 expression of oho31 by a P element inserted in the 5' untranslated region of the oho31 transcript or a complete inactivation of oho31 by imprecise P element excision leads to malignant development of the hematopoietic organs and the genital disc, as shown by their growth autonomy in transplantation assays. We have cloned the oho31 gene of Drosophila melanogaster and determined its nucleotide sequence. The gene encodes a phosphoprotein of 522 amino acids made of three domains: a central hydrophobic domain of eight repeats of 42-44 amino acids each, displaying similarity to the arm motif found in junctional and nucleopore complex proteins, and flanked by two hydrophilic NH2-and COOH-terminal domains. Immunostaining revealed that the 0H031 protein is supplied maternally and rapidly degraded during the first 13 nuclear divisions. Thereafter, the 0H031 protein is predominantly expressed, albeit at reduced levels, in proliferating tissues. During the interphase of early embryonic cell cycles, the 0H031 protein is present in the cytoplasm and massively accumulates in the nucleus at the onset of mitosis in late interphase and prophase. The nuclear import of 0H031 is, however, less pronounced during later developmental stages. These results suggest that, similar to Importin, 0H031 may act as a cytosolic factor in nuclear transport. Moreover, the cell cycle-dependent accumulation of 0H031 in the nucleus indicates that this protein may be required for critical nuclear reactions occurring at the onset of mitosis.

Differential Importin-α Recognition and Nuclear Transport by Nuclear Localization Signals within the High-Mobility-Group DNA Binding Domains of Lymphoid Enhancer Factor 1 and T-Cell Factor 1

“…These two receptors, variously referred to as importin-␣/pendulin/Rch1/ hSrp1␣/␣-P1/PTAC58/karyopherin ␣2 (9,16,21,25,49,56) and Srp1/karyopherin-␣/NPI-1/␣-S1 (8,34,36,58), bind directly to NLSs and, along with a second, armadillo repeatcontaining subunit (importin-␤/p97/karyopherin-␤) (8), dock the NLS-bearing substrate at the nuclear pore (7,14,21,40,56). Subsequent transport steps are GTP/GDP dependent and involve movement of the NLS receptor and NLS-bearing substrate together as a complex through the pore into the nucleoplasm (2,15,32,35).…”

A Role forCaenorhabditis elegansImportin IMA-2 in Germ Line and Embryonic Mitosis

“…cut15-85 mutants do not have gross defects in nuclear protein import, suggesting that the cut phenotype is not due to failure in protein import. The Drosophila melanogaster importin ␣2 pendulin may also have a direct role in mitosis because it accumulates in embryonic nuclei at the onset of mitosis (Kussel and Frasch, 1995a;Torok et al, 1995). Although these results have been suggestive of a nontransport role in mitosis for members of the importin ␣ family, only the sequestration and release of TPX2 from importin ␣ to regulate mitotic spindle assembly has been directly implicated in a mitotic function (Gruss et al, 2001).…”

“…Drosophila melanogaster pendulin (an ␣2) and S. pombe Cut15p (an ␣1) exhibit a similar mitotic nuclear localization. Pendulin accumulates rapidly in the nucleus at the onset of prophase of early embryos (Kussel and Frasch, 1995a;Torok et al, 1995). The intensity of nuclear staining decreases through metaphase and anaphase and increases again at telophase.…”

Nuclear Pore-Targeting Complex and Its Role on Nuclear Protein Transport.

“…PTAC 58 showed a 93% amino acid identity with human Rchl, 61% with Xenopus importin a (GORLICH et al, 1994), 52% with Drosophila pendulin (overgrown hematopoietic organs-31; oho 31) (TOROK et al, 1995;KUSSEL and FRASCH, 1995), and 46% with yeast Srplp (YANO et al, 1992). These proteins contain central tandem repeats known as the arm motif, which was first identified in the Drosophila segment polarity gene armadillo (RIGGLEMAN et al, 1989).…”

“…Recently, it was found that Srpl exists in yeast cytosol in a complex with an essential homologue of karyopherin 3 (PTAC 97) (ENENKEL et al, 1995). Drosophila pendulin was identified as the tumor suppresser gene and its subcellular localization in proliferating tissues was of interest (TOROK et al, 1995;KUSSEL and FRASCH, 1995). That is, during the interphase, the protein is present in the cytoplasm but accumulates in the nucleus at the onset of mitosis.…”