The Requirement of H1 Histones for a Heterodimeric Nuclear Import Receptor

Abstract The majority of lncRNAs and a small fraction of mRNAs localize in the cell nucleus to exert their functions. A SIRLOIN RNA motif was previously reported to drive its nuclear localization by the RNA-binding protein hnRNP K. However, the underlying mechanism remains unclear. Here, we report crystal structures of hnRNP K in complex with SIRLOIN, and with the nuclear import receptor (NIR) Impα1, respectively. The protein hnRNP K bound to SIRLOIN with multiple weak interactions, and interacted Impα1 using an independent high-affinity site. Forming a complex with hnRNP K and Impα1 was essential for the nuclear and stress granule localization of SIRLOIN in semi-permeabilized cells. Nuclear import of SIRLOIN enhanced with increasing NIR concentrations, but its stress granule localization peaked at a low NIR concentration. Collectively, we propose a mechanism of SIRLOIN localization, in which NIRs functioned as drivers/regulators, and hnRNP K as an adaptor.

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The Nuclear Import Receptor Kpnβ1 and Its Potential as an AntiCancer Therapeutic Target

Critical Reviews in Eukaryotic Gene Expression ◽

10.1615/critreveukargeneexpr.2013004845 ◽

2013 ◽

Vol 23 (1) ◽

pp. 1-10 ◽

Cited By ~ 23

Author(s):

Pauline J. van der Watt ◽

Catherine L. Stowell ◽

Virna D. Leaner

Keyword(s):

Nuclear Import ◽

Therapeutic Target ◽

Import Receptor

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The ubiquitin-conjugating enzyme UBE2E3 and its import receptor importin-11 regulate the localization and activity of the antioxidant transcription factor NRF2

Molecular Biology of the Cell ◽

10.1091/mbc.e14-06-1057 ◽

2015 ◽

Vol 26 (2) ◽

pp. 327-338 ◽

Cited By ~ 15

Author(s):

Kendra S. Plafker ◽

Scott M. Plafker

Keyword(s):

Transcription Factor ◽

Nuclear Import ◽

Target Gene ◽

Redox Homeostasis ◽

Related Factor ◽

Gene Promoters ◽

Nrf2 Target Gene ◽

Ubiquitin Conjugating Enzyme ◽

Import Receptor ◽

Conjugating Enzyme

The transcription factor NF-E2 p45–related factor (Nrf2) induces the expression of cytoprotective proteins that maintain and restore redox homeostasis. Nrf2 levels and activity are tightly regulated, and three subcellular populations of the transcription factor have been identified. During homeostasis, the majority of Nrf2 is degraded in the cytoplasm by ubiquitin (Ub)-mediated degradation. A second population is transcriptionally active in the nucleus, and a third population localizes to the outer mitochondrial membrane. Still unresolved are the mechanisms and factors that govern Nrf2 distribution between its subcellular locales. We show here that the Ub-conjugating enzyme UBE2E3 and its nuclear import receptor importin 11 (Imp-11) regulate Nrf2 distribution and activity. Knockdown of UBE2E3 reduces nuclear Nrf2, decreases Nrf2 target gene expression, and relocalizes the transcription factor to a perinuclear cluster of mitochondria. In a complementary manner, Imp-11 functions to restrict KEAP1, the major suppressor of Nrf2, from prematurely extracting the transcription factor off of a subset of target gene promoters. These findings identify a novel pathway of Nrf2 modulation during homeostasis and support a model in which UBE2E3 and Imp-11 promote Nrf2 transcriptional activity by restricting the transcription factor from partitioning to the mitochondria and limiting the repressive activity of nuclear KEAP1.

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