The influenza virus replicates in the host cell nucleus, and the progeny viral ribonucleoprotein complex (vRNP) is exported to the cytoplasm prior to maturation. NS2 has a nuclear export signal that mediates the nuclear export of vRNP by the vRNP-M1-NS2 complex. We previously reported that the heat shock cognate 70 (Hsc70) protein binds to M1 protein and mediates vRNP export. However, the interactions among M1, NS2, and Hsc70 are poorly understood. In the present study, we demonstrate that Hsc70 interacts with M1 more strongly than with NS2 and competes with NS2 for M1 binding, suggesting an important role of Hsc70 in the nuclear export of vRNP.
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http://dx.doi.org/10.1016/j.fob.2014.07.004 | DOI Listing |
Cell Mol Life Sci
January 2025
Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Unitat de Farmacologia, Universitat de Barcelona, Av. Joan XXIII 27-31, 08028, Barcelona, Spain.
Nuclear growth differentiation factor 15 (GDF15) reduces the binding of the mothers' against decapentaplegic homolog (SMAD) complex to its DNA-binding elements. However, the stimuli that control this process are unknown. Here, we examined whether saturated fatty acids (FA), particularly palmitate, regulate nuclear GDF15 levels and the activation of the SMAD3 pathway in human skeletal myotubes and mouse skeletal muscle, where most insulin-stimulated glucose use occurs in the whole organism.
View Article and Find Full Text PDFCell Rep
January 2025
Department of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Center for Biophysics and Quantitative Biology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Carle Illinois College of Medicine, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA. Electronic address:
The influenza A virus nuclear export protein (NEP) is a multifunctional protein that is essential for the viral life cycle and has very high sequence conservation. However, since the open reading frame of NEP largely overlaps with that of another influenza viral protein, non-structural protein 1, it is difficult to infer the functional constraints of NEP based on sequence conservation analysis. In addition, the N-terminal of NEP is structurally disordered, which further complicates the understanding of its function.
View Article and Find Full Text PDFJ 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 PDFRNA
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.
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