TY - JOUR
T1 - A microtubule-facilitated nuclear import pathway for cancer regulatory proteins
AU - Martino Roth, Daniela
AU - Moseley, Gregory William
AU - Glover, Dominic
AU - Pouton, Colin William
AU - Jans, David Andrew
N1 - M1 - 6
Roth, Daniela Martino Moseley, Gregory W Glover, Dominic Pouton, Colin W Jans, David A eng Research Support, Non-U.S. Gov't Denmark Copenhagen, Denmark 2007/05/22 09:00 Traffic. 2007 Jun;8(6):673-86.
PY - 2007
Y1 - 2007
N2 - Nuclear protein import is dependent on specific targeting signals within cargo proteins recognized by importins (IMPs) that mediate translocation through the nuclear pore. Recent evidence, however, implicates a role for the microtubule (MT) network in facilitating nuclear import of the cancer regulatory proteins parathyroid hormone-related protein (PTHrP) and p53 tumor suppressor. Here we assess the extent to which MT and actin integrity may be generally required for nuclear protein import for the first time. We examine 10 nuclear-localizing proteins with diverse IMP-dependent nuclear import pathways, our results indicating that the cytoskeleton does not have a general mechanistic role in nuclear localization sequence-dependent nuclear protein import. Of the proteins examined, only the p110(Rb) tumor suppressor protein Rb, together with p53 and PTHrP, was found to require MT integrity for optimal nuclear import. Fluorescence recovery after photobleaching experiments indicated that the MT-dependent nuclear transport pathway increases both the rate and extent of Rb nuclear import but does not affect Rb nuclear export. Dynamitin overexpression experiments implicate the MT motor dynein in the import process. The results indicate that, additional to IMP/diffusion-dependent processes, certain cancer regulatory proteins utilize an MT-enhanced pathway for accelerated nuclear import that is presumably required for their nuclear functions.
AB - Nuclear protein import is dependent on specific targeting signals within cargo proteins recognized by importins (IMPs) that mediate translocation through the nuclear pore. Recent evidence, however, implicates a role for the microtubule (MT) network in facilitating nuclear import of the cancer regulatory proteins parathyroid hormone-related protein (PTHrP) and p53 tumor suppressor. Here we assess the extent to which MT and actin integrity may be generally required for nuclear protein import for the first time. We examine 10 nuclear-localizing proteins with diverse IMP-dependent nuclear import pathways, our results indicating that the cytoskeleton does not have a general mechanistic role in nuclear localization sequence-dependent nuclear protein import. Of the proteins examined, only the p110(Rb) tumor suppressor protein Rb, together with p53 and PTHrP, was found to require MT integrity for optimal nuclear import. Fluorescence recovery after photobleaching experiments indicated that the MT-dependent nuclear transport pathway increases both the rate and extent of Rb nuclear import but does not affect Rb nuclear export. Dynamitin overexpression experiments implicate the MT motor dynein in the import process. The results indicate that, additional to IMP/diffusion-dependent processes, certain cancer regulatory proteins utilize an MT-enhanced pathway for accelerated nuclear import that is presumably required for their nuclear functions.
KW - Active Transport, Cell Nucleus Animals COS Cells Cell Line, Tumor Cercopithecus aethiops Humans Karyopherins/metabolism Microtubules/metabolism Parathyroid Hormone-Related Protein/metabolism Retinoblastoma Protein/metabolism Tumor Suppressor Protein p53/m
UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17511743
U2 - 10.1111/j.1600-0854.2007.00564.x
DO - 10.1111/j.1600-0854.2007.00564.x
M3 - Article
VL - 8
SP - 673
EP - 686
JO - Traffic
JF - Traffic
SN - 1398-9219
IS - 6
ER -