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Lookup NU author(s): Professor Jane Endicott
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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
Journal: Cell
Year: 2014
Volume: 157
Issue: 5
Pages: 1130-1145
Print publication date: 22/05/2014
ISSN (print): 0092-8674
ISSN (electronic): 1097-4172
Publisher: Cell Press
URL: http://dx.doi.org/10.1016/j.cell.2014.05.006
DOI: 10.1016/j.cell.2014.05.006
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