Enhancement of protein transduction-mediated nuclear delivery by interaction with dynein/microtubules.
Nucleocytoplasmic trafficking is a major consideration for the design of vehicles for the delivery of drug/DNA cargo to cell nuclei for cancer and gene therapies. Recent data indicate that efficient nuclear import can involve the microtubule (MT)/dynein network, such that nuclear delivery of exogenous cargo could be enhanced by attachment to peptide modules mediating association with dynein components, but this has not been investigated. Here, we report that the nuclear delivery of an exogenous cargo that enters the cell by protein transduction can be enhanced by attachment to a dynein-association sequence, with dependence on the MT network. This indicates that dynein/MT-association modules may provide useful modules for DNA/drug delivery approaches.
Moseley
Gregory W
GW
Nuclear Signalling Laboratory, Dept. of Biochemistry and Molecular Biology, Monash University, Monash, Vic. 3800, Australia. greg.moseley@med.monash.edu.au
Leyton
Denisse L
DL
Glover
Dominic J
DJ
Filmer
Richard P
RP
Jans
David A
DA
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000378:metabolism*; D004398:Dyneins / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006639:Histidine / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014161:Transduction, Genetic / Q000379:methods*
C471213:His-His-His-His-His-His; D006657:Histones; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D006639:Histidine; D004398:Dyneins