In vivo analysis of importin α proteins reveals cellular proliferation inhibition and substrate specificity

Christina Quensel, Beate Friedrich, Thomas Sommer, Enno Hartmann, Matthias Kohler*

*Korrespondierende/r Autor/-in für diese Arbeit
64 Zitate (Scopus)

Abstract

The "classical" nuclear import pathway depends on importins α and β. Humans have only one importin β, while six α importins have been described. Whether or not distinct α 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 α importins in HeLa cells. Down-regulation of importins α3, α5, α7, and β strongly inhibited HeLa cell proliferation, while down-regulation of importins α1 and α4 had only a minor effect or no effect. Nucleoplasmin import was not prevented by down-regulation of any α importin, indicating that the importin α/β pathway was generally not affected. In contrast, importin α3 or α5 down-regulation specifically inhibited the nuclear import of the Ran guanine nucleotide exchange factor, RCC1. Coinjection of recombinant α importins and RCC1 into down-regulated cells demonstrated that these transport defects were specifically caused by the limited availability of importin α3 in both cases. Thus, importin α3 is the only α importin responsible for the classical nuclear import of RCC1 in living cells.

OriginalspracheEnglisch
ZeitschriftMolecular and Cellular Biology
Jahrgang24
Ausgabenummer23
Seiten (von - bis)10246-10255
Seitenumfang10
ISSN0270-7306
DOIs
PublikationsstatusVeröffentlicht - 01.12.2004

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