Importins and exportins in cellular differentiation

Okada, Naoya; Ishigami, Yoko; Suzuki, Takuji; Kaneko, Akihiro; Yasui, Kensuke; Fukutomi, Ryuuta; Isemura, Mamoru

doi:10.1111/j.1582-4934.2008.00437.x

Cited by 41 publications

(40 citation statements)

References 77 publications

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“…This constitutes the first report identifying IPO9 as a regulator of IFN-ε mRNA expression, a function suggesting roles additional to those previously reported. Importins, including IPO9, are known for their ability to mediate active transport through nuclear pore complexes (29) and effectively suppress the aggregation of their basic import cargoes in polyanionic environments (15). Importins exert their functions through protein-protein interactions; they recognize nuclear localization signalsand prevent protein aggregation by shielding basic patches such as those found in a variety of ribosomal proteins (15).…”

Section: Discussionmentioning

confidence: 99%

Novel Role for Molecular Transporter Importin 9 in Posttranscriptional Regulation of IFN-ε Expression

Matsumiya

Xing

Ebina

et al. 2013

The Journal of Immunology

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IFN-ε is a unique type-I interferon (IFN)whose constitutive expression inlung, brain, small intestine, and reproductive tissuesis only partiallyunderstood. Our previous observationthat post-transcriptional events participate in the regulation of IFN-εmRNA expression led us to investigate whether the 5′ and/or 3′un-translated regions (UTR)have regulatory functions. Surprisingly, we found that full-length IFN-ε 5′UTR markedly suppressed mRNA expression under basal conditions. Analysis of the secondary structure of this regionpredicted formation of two stable stem loop-structures, loops 1 and 2. Studies using luciferase constructs harboring various stretches of IFN-ε 5′UTR and mutant constructs in whichthe conformation of loop structures was disrupted showed that loop 1 is essential forregulation of mRNA expression. Incubation of HeLa cell extracts with agarose bound-RNAs harboring IFN-ε loop structures identified importin 9 (IPO9), a molecular transporter and chaperone, as a candidate that associates with these region of the 5′UTR. IPO9 overexpression decreased, and IPO9 silencing increased, basal IFN-ε expression. Our studies uncover a previously undescribedfunction for IPO9 as a specific, and negative, post-transcriptional regulator of IFN-ε expression and they identify key roles for IFN-ε stem loop structure 1 in this process. IPO9-mediated effects on 5′UTRs appear to extend to additional mRNAs, including HIF-1α, that can form specific loop structures.

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Section: Discussionmentioning

confidence: 99%

Novel Role for Molecular Transporter Importin 9 in Posttranscriptional Regulation of IFN-ε Expression

Matsumiya

Xing

Ebina

et al. 2013

The Journal of Immunology

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“…Regulation of protein transport across the NPC, and the kinetics thereof, plays a central role in controlling cellular processes such as cell growth and differentiation, and response to pathogens [45]. In the case of transcription factors, this can determine whether a critical intranuclear concentration is achieved or not, thus ultimately determining its effect on cellular transcription [46].…”

Section: Regulation Of Nuclear Transportmentioning

confidence: 99%

Regulated Transport into the Nucleus of Herpesviridae DNA Replication Core Proteins

Alvisi

Jans

Camozzi

et al. 2013

Viruses

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The Herpesvirdae family comprises several major human pathogens belonging to three distinct subfamilies. Their double stranded DNA genome is replicated in the nuclei of infected cells by a number of host and viral products. Among the latter the viral replication complex, whose activity is strictly required for viral replication, is composed of six different polypeptides, including a two-subunit DNA polymerase holoenzyme, a trimeric primase/helicase complex and a single stranded DNA binding protein. The study of herpesviral DNA replication machinery is extremely important, both because it provides an excellent model to understand processes related to eukaryotic DNA replication and it has important implications for the development of highly needed antiviral agents. Even though all known herpesviruses utilize very similar mechanisms for amplification of their genomes, the nuclear import of the replication complex components appears to be a heterogeneous and highly regulated process to ensure the correct spatiotemporal localization of each protein. The nuclear transport process of these enzymes is controlled by three mechanisms, typifying the main processes through which protein nuclear import is generally regulated in eukaryotic cells. These include cargo post-translational modification-based recognition by the intracellular transporters, piggy-back events allowing coordinated nuclear import of multimeric holoenzymes, and chaperone-assisted nuclear import of specific subunits. In this review we summarize these mechanisms and discuss potential implications for the development of antiviral compounds aimed at inhibiting the Herpesvirus life cycle by targeting nuclear import of the Herpesvirus DNA replicating enzymes.

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“…Therefore, the nuclear transport system critically contributes to regulating cellular homeostasis. It is also involved in key events during development (Yasuhara et al , 2007; Okada et al , 2008) and malignant transformation (Winkler et al , 2016). Indeed various clinically manifested mutations map into components of the nuclear transport system, and alterations of transport pathways have been linked to various human diseases (reviewed in Kimura & Imamoto, 2014).…”

Section: Introductionmentioning

confidence: 99%

Landscape of nuclear transport receptor cargo specificity

Mackmull

Klaus

Heinze

et al. 2017

Molecular Systems Biology

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Nuclear transport receptors (NTRs) recognize localization signals of cargos to facilitate their passage across the central channel of nuclear pore complexes (NPCs). About 30 different NTRs constitute different transport pathways in humans and bind to a multitude of different cargos. The exact cargo spectrum of the majority of NTRs, their specificity and even the extent to which active nucleocytoplasmic transport contributes to protein localization remains understudied because of the transient nature of these interactions and the wide dynamic range of cargo concentrations. To systematically map cargo–NTR relationships in situ, we used proximity ligation coupled to mass spectrometry (BioID). We systematically fused the engineered biotin ligase BirA* to 16 NTRs. We estimate that a considerable fraction of the human proteome is subject to active nuclear transport. We quantified the specificity and redundancy in NTR interactions and identified transport pathways for cargos. We extended the BioID method by the direct identification of biotinylation sites. This approach enabled us to identify interaction interfaces and to discriminate direct versus piggyback transport mechanisms. Data are available via ProteomeXchange with identifier PXD007976.

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Importins and exportins in cellular differentiation

Cited by 41 publications

References 77 publications

Novel Role for Molecular Transporter Importin 9 in Posttranscriptional Regulation of IFN-ε Expression

Novel Role for Molecular Transporter Importin 9 in Posttranscriptional Regulation of IFN-ε Expression

Regulated Transport into the Nucleus of Herpesviridae DNA Replication Core Proteins

Landscape of nuclear transport receptor cargo specificity

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