Browse by author
Lookup NU author(s): Professor Jane Endicott
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Regulation of nuclear import is fundamental to eukaryotic biology. The majority of nuclear import pathways are mediated by importin-cargo interactions. Yet not all nuclear proteins interact with importins, necessitating the identification of a general importin-independent nuclear import pathway. Here, we identify a code that determines importin-independent nuclear import of ankyrin repeats (ARs), a structural motif found in over 250 human proteins with diverse functions. AR-containing proteins (ARPs) with a hydrophobic residue at the 13th position of two consecutive ARs bind RanGDP efficiently, and consequently enter the nucleus. This code, experimentally tested in 17 ARPs, predicts the nuclear-cytoplasmic localization of over 150 annotated human ARPs with high accuracy and is acquired by the most common familial melanoma-associated CDKN2A mutation, leading to nuclear accumulation of mutant p16ink4a. The RaDAR (RanGDP/AR) pathway represents a general importin-independent nuclear import pathway and is frequently used by AR-containing transcriptional regulators, especially those regulating NF-kappa B/p53.
Author(s): Lu M, Zak J, Chen SO, Sanchez-Pulido L, Severson DT, Endicott J, Ponting CP, Schofield CJ, Lu X
Publication type: Article
Publication status: Published
Print publication date: 22/05/2014
ISSN (print): 0092-8674
ISSN (electronic): 1097-4172
Publisher: Cell Press
Altmetrics provided by Altmetric