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The nuclear import of classical nuclear localization signal-containing proteins depends on importin-[alpha] transport receptors. In budding yeast there is a single importin-[alpha] gene and in higher eukaryotes there are multiple importin-[alpha]-like genes, but in fission yeast there are two: the previously characterized cut15 and the more recently identified imp1. Like other importin-[alpha] family members, Imp1p supports nuclear protein import in vitro. In contrast to cut15, imp1 is not essential for viability, but imp1[DELTA] mutant cells exhibit a telophase delay and mild temperature-sensitive lethality. Differences in the cellular functions that depend on Imp1p and Cut15p indicate that they each have unique physiological roles. They also have common roles because the imp1[DELTA] and the cut15-85 temperature-sensitive mutations are synthetically lethal; overexpression of cut15 partially suppresses the temperature sensitivity, but not the mitotic delay in imp1[DELTA] cells; and overexpression of imp1 partially suppresses the mitotic defect in cut15-85 cells but not the loss of viability. Both Imp1p and Cut15p are required for the efficient nuclear import of both an SV40 nuclear localization signal-containing reporter protein and the Pap1p component of the stress response MAP kinase pathway. Imp1p and Cut15p are essential for efficient nuclear protein import in S. pombe.

Nup98, a nuclear pore complex (NPC) protein of rat, has been identified as a new mammalian member of the nucleoporin family, one which has many GLFG and FG repeat sequences. It is located in the nucleoplasmic site of the NPC, and the N-terminal repeat sequences have been reported to be involved in the cytosol-dependent binding of the ligand. The repeat sequences thus act as docking sites, where transport across NPC takes place by docking and un-docking reactions at these sites. Molecular characterization of this protein has also been reported.

P10 is the new and second protein essential for the activity of fraction B in transporting proteins to the digitonin-permeabilized cell nuclei of Xenopus ovary. Gel filtration chromatography and SDS/PAGE methods indicate that the peptide sequence of P10 is similar to the human placental protein 15 and to the protein product of Saccharomyces cerevisiae open reading frame. P10 fractionates with a size of 30 kDa but exhibits a 10 kDa molecular mass with gel chromatography. P10 coordinates with the first protein GTPase ras-related nuclear protein to enhance fraction B activity.

Ran is the only known member of the Ras superfamily of small GTP-binding proteins to be localized primarily inside the nucleus. Recently, Ran was unexpectedly identified as one of the soluble factors required for nuclear import. As this protein has also been implicated in RNA export, nuclear import and export may be more closely related than previously thought, with Ran playing a key role in each.

Protein import into the nuclei of digitonin permeabilized cells is supported by the A and B cytosolic fractions from Xenopus oocytes. The nuclear localization sequence is recognized by the fraction A, which supports the import to the nuclear envelope. The consequent movement of the binding substrates into the nucleus is mediated by the fraction B. The activity of the fraction B requires two interacting constituents. The purification of one of these constituents to homogeneity reveals that it is made up of the GTP-binding protein Ran/TC4, which is abundant in the human body.

Simian virus 40 (SV40) is a DNA tumor virus known to induce cancers in laboratory animals. There are numerous reports of the detection of SV40 DNA and/or proteins in human malignancies of the same types as those induced by SV40 in animals, including brain cancers. However, known exposure to the virus has not yet been linked directly to cancer development in a specific individual. Here we describe the detection of SV40 sequences in the meningioma of a laboratory researcher who had a probable direct exposure to SV40 and subsequently developed a tumor positive for viral DNA sequences indistinguishable from those of the laboratory source. This case suggests a link between viral exposure and tumor development.Oncogene (2004) 23, 2231-2235. doi:10.1038/sj.onc.1207341 Published online 15 December 2003 [ABSTRACT FROM AUTHOR]

The nuclear import of classical nuclear localization signal-containing proteins depends on importin-α transport receptors. In budding yeast there is a single importin-α gene and in higher eukaryotes there are multiple importin-α-like genes, but in fission yeast there are two: the previously characterized cut15 and the more recently identified imp1. Like other importin-α family members, Imp1p supports nuclear protein import in vitro. In contrast to cut15, imp1 is not essential for viability, but imp1Δ mutant cells exhibit a telophase delay and mild temperature-sensitive lethality. Differences in the cellular functions that depend on Imp1p and Cut15p indicate that they each have unique physiological roles. They also have common roles because the imp1Δ and the cut15-85 temperature-sensitive mutations are synthetically lethal; overexpression of cut15 partially suppresses the temperature sensitivity, but not the mitotic delay in imp1Δ cells; and overexpression of imp1 partially suppresses the mitotic defect in cut15-85 cells but not the loss of viability. Both Imp1p and Cut15p are required for the efficient nuclear import of both an SV40 nuclear localization signal-containing reporter protein and the Pap1p component of the stress response MAP kinase pathway. Imp1p and Cut15p are essential for efficient nuclear protein import in S. pombe. [ABSTRACT FROM AUTHOR]