2004
DOI: 10.1128/mcb.24.23.10246-10255.2004
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In Vivo Analysis of Importin α Proteins Reveals Cellular Proliferation Inhibition and Substrate Specificity

Abstract: The "classical" nuclear import pathway depends on importins ␣ and ␤. Humans have only one importin ␤, while six ␣ importins have been described. Whether or not distinct ␣ importins are essential for specific import pathways in living human cells is unclear. We used RNA interference technology to specifically down-regulate the expression of ubiquitously expressed human ␣ importins in HeLa cells. Down-regulation of importins ␣3, ␣5, ␣7, and ␤ strongly inhibited HeLa cell proliferation, while down-regulation of i… Show more

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Cited by 79 publications
(88 citation statements)
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“…We believe that importin ␣4 can function much in the same way in NF-B interactions as importin ␣3. It is likely that these importins also have distinct substrate specificities (45,64).…”
Section: Discussionmentioning
confidence: 99%
“…We believe that importin ␣4 can function much in the same way in NF-B interactions as importin ␣3. It is likely that these importins also have distinct substrate specificities (45,64).…”
Section: Discussionmentioning
confidence: 99%
“…An exception is the spermatogenesis defect of Da2 mutant flies that is rescued by any of the three paralogs (Mason et al 2002). It is established that importin a1's each have both shared and distinct cargo repertoires (Michaud and Goldfarb 1993;Prieve et al 1996;Miyamoto et al 1997;Prieve et al 1998;Kohler et al 1999;Talcott and Moore 2000;Fagerlund et al 2002;Quensel et al 2004;Lange et al 2007). The simplest explanations for the paralog-specific phenotypes associated with Da1, Da2, and Da3 mutants invoke deficiencies in the nuclear import of their distinct NLS cargoes.…”
Section: Discussionmentioning
confidence: 99%
“…Although importin a1, a2, and a3 proteins are coexpressed in many adult tissues, they exhibit complex temporal and spatial expression patterns during development (see Kamei et al 1999;Hogarth et al 2006). Animal importin a1's, a2's, and a3's all mediate the import of classical NLS-containing cargoes and, in addition, each paralog is specialized to bind and mediate the import of distinct repertoires of NLS cargoes (for example, see Michaud and Goldfarb 1993;Prieve et al 1996;Miyamoto et al 1997;Prieve et al 1998;Kohler et al 1999;Talcott and Moore 2000;Fagerlund et al 2002;Quensel et al 2004;Lange et al 2007). Importin a's may also mediate the import of a few cargoes independent of b1 (Hubner et al 1999;Miyamoto et al 2002;Kotera et al 2005).…”
mentioning
confidence: 99%
“…Macromolecules such as RNA transcripts generated in the nucleus are exported from the nucleus to the ribosomes in the cytoplasm, and proteins synthesized in the cytoplasm, such as histones, polymerases, and transcription factors, are imported into the nucleus. The importin/exportin transport system is involved in the nucleocytoplasmic transport of such cargo molecules (1)(2)(3)(4)(6)(7)(8). In this system, proteins to be imported or exported have generally a nuclear localization signal (NLS) sequence or a nuclear export signal (NES) sequence.…”
mentioning
confidence: 99%