Background: The human immunodeficiency virus type 1 (HIV-1) regulatory protein Rev is required for unspliced and incompletely spliced viral mRNAs to appear in the cytoplasm and thus for viral replication. Translocation of Rev from the nucleus to the cytoplasm is essential if Rev is to function. We wanted to identify inhibitors of this transport process because they would be potential antiviral agents.
Results: The Streptomyces metabolite, leptomycin B, and other antibiotics of the leptomycin/kazusamycin family were identified as inhibitors of the nucleo-cytoplasmic translocation of Rev at nanomolar concentrations. Rev-dependent export of mRNA into the cytoplasm is also blocked by leptomycin B, which inhibits Rev-dependent, but not Rev-independent gene expression in a short-term transfection assay. In primary human monocytes, leptomycin B suppresses HIV-1 replication.
Conclusions: Leptomycin B is the first low molecular weight inhibitor of nuclear export to be identified. Although it cannot be used therapeutically, it should serve as a valuable tool for dissecting nuclear export pathways.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s1074-5521(97)90257-x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Enhanced kinase translocation reporters for simultaneous real-time measurement of PKA, ERK, and calcium.
J Biol Chem
January 2025
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA. Electronic address:
Kinase translocation reporters (KTRs) are powerful tools for single-cell measurement of time-integrated kinase activity but suffer from restricted dynamic range and limited sensitivity, particularly in neurons. To address these limitations, we developed enhanced KTRs (eKTRs) for protein kinase A (PKA) and extracellular signal-regulated kinase (ERK) by (i) increasing KTR size, which reduces the confounding effect of KTR diffusion through the nuclear pore, and (ii) modulating the strength of the bipartite nuclear localization signal (bNLS) in their kinase sensor domains, to ensures that the relative distribution of the KTR between the nucleus and cytoplasmic is determined by active nuclear import, active nuclear export, and relative activity of their cognate kinase. The resultant sets of ePKA-KTRs and eERK-KTRs display high sensitivity, broad dynamic range, and cell type-specific tuning.
View Article and Find Full Text PDFNUCLEAR RNA-BINDING PROTEINS MEET CYTOPLASMIC VIRUSES.
RNA
January 2025
MRC University of Glasgow Centre for Virus Research, University of Glasgow.
Cytoplasmic viruses interact intricately with the nuclear pore complex and nuclear import/export machineries, affecting nuclear-cytoplasmic trafficking. This can lead to the selective accumulation of nuclear RNA-binding proteins (RBPs) in the cytoplasm. Pioneering research has shown that relocated RBPs serve as an intrinsic defence mechanism against viruses, which involves RNA export, splicing and nucleolar factors.
View Article and Find Full Text PDFThe nuclear pore complex (NPC), a multisubunit complex located within the nuclear envelope, regulates RNA export and the import and export of proteins. Here we address the role of the NPC in driving thermal stress-induced 3D genome repositioning of ( ) genes in yeast. We found that two nuclear basket proteins, Mlp1 and Nup2, although dispensable for NPC integrity, are required for driving genes into coalesced chromatin clusters, consistent with their strong, heat shock-dependent recruitment to gene regulatory and coding regions.
View Article and Find Full Text PDFUnveiling the Movement of RanBP1 During the Cell Cycle and Its Interaction with a Cyclin-Dependent Kinase (CDK) in Plants.
Int J Mol Sci
December 2024
Departamento de Biologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto 14040-901, SP, Brazil.
In the flower development study, we identified SCI1 (Stigma/style Cell-cycle Inhibitor 1), a regulator of cell proliferation. SCI1 interacts with NtCDKG;2 ( Cyclin-Dependent Kinase G;2), a homolog of human CDK11, which is responsible for RanGTP-dependent microtubule stabilization, regulating spindle assembly rate. In a Y2H screening of a cDNA library using NtCDKG;2 as bait, a RanBP1 (Ran-Binding Protein 1) was revealed as its interaction partner.
View Article and Find Full Text PDFThe pseudorabies virus UL13 protein kinase triggers phosphorylation of the RNA demethylase FTO, which is associated with FTO-dependent suppression of interferon-stimulated gene expression.
J Virol
January 2025
Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Alpha-ketoglutarate-dependent dioxygenase, also known as fat mass and obesity-associated protein (FTO), is an RNA demethylase that mediates the demethylation of N,2-O-dimethyladenosine (m6Am) and N-methyladenosine (m6A). Both m6Am and m6A are prevalent modifications in mRNA and affect different aspects of transcript biology, including splicing, nuclear export, translation efficiency, and degradation. The role of FTO during (herpes) virus infection remains largely unexplored.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!