Affiliation:
1. Cell and Molecular Biology Graduate Group,1
2. Departments of Microbiology 2 and
3. Medicine, 3 and
4. Howard Hughes Medical Institute, 4 University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148
Abstract
ABSTRACT
The import of proteins into the nucleus is dependent on
cis
-acting targeting sequences, nuclear localization signals (NLSs), and members of the nuclear transport receptor (importin-β-like) superfamily. The most extensively characterized import pathway, often termed the classical pathway, is utilized by many basic-type (lysine-rich) NLSs and requires an additional component, importin α, to serve as a bridge between the NLS and the import receptor importin β. More recently, it has become clear that a variety of proteins enter the nucleus via alternative import receptors and that their NLSs bind directly to those receptors. By using the digitonin-permeabilized cell system for protein import in vitro, we have defined the import pathway for the Rex protein of human T-cell leukemia virus type 1. Interestingly, the arginine-rich NLS of Rex uses importin β for import but does so by a mechanism that is importin α independent. Based on the ability of the Rex NLS to inhibit the import of the lysine-rich NLS of T antigen and of both NLSs to be inhibited by the domain of importin α that binds importin β (the IBB domain), we infer that the Rex NLS interacts with importin β directly. In addition, and in keeping with other receptor-mediated nuclear import pathways, Rex import is dependent on the integrity of the Ran GTPase cycle. Based on these results, we suggest that importin β can mediate the nuclear import of arginine-rich NLSs directly, or lysine-rich NLSs through the action of importin α.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Cited by
168 articles.
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