Disease relevance of Active Transport, Cell Nucleus

• The Rev protein acts posttranscriptionally to induce the sequence-specific nuclear export of unspliced HIV-1 mRNA species that are otherwise excluded from the cell cytoplasm [1].
• HIV nuclear import is governed by the phosphotyrosine-mediated binding of matrix to the core domain of integrase [2].
• The past year has been marked by the discovery that the influenza virus NS1 protein belongs to the group of viral proteins that regulate the nuclear export of mRNA [3].
• While it has been shown that the matrix (M) protein of the vesicular stomatitis virus (VSV) inhibits nuclear export of host cell mRNAs, the underlying mechanism has not been fully established [4].
• Up-regulation, nuclear import, and tumor growth stimulation of the adhesion protein p120 in pancreatic cancer [5].

High impact information on Active Transport, Cell Nucleus

• Moreover, these studies have revealed unanticipated roles for the RNA polymerase II elongation complex in such processes as DNA repair and recombination and the proper processing and nucleocytoplasmic transport of mRNA [6].
• The Ras family regulates gene expression, the Rho family regulates cytoskeletal reorganization and gene expression, the Rab and Sar1/Arf families regulate vesicle trafficking, and the Ran family regulates nucleocytoplasmic transport and microtubule organization [7].
• Phosphorylation appears to be the main mechanism controlling the nuclear transport of a number of proteins, including transcription factors such as NFkappaB, c-rel, dorsal, and SWI5 from yeast [8].
• Polyglutamine expansion of huntingtin impairs its nuclear export [9].
• Small N-terminal htt fragments interact with the nuclear pore protein translocated promoter region (Tpr), which is involved in nuclear export [9].

Chemical compound and disease context of Active Transport, Cell Nucleus

• The HIV-1 proteins Matrix, Vpr and Integrase have been implicated in the nuclear import of the viral genome in non-dividing cells [10].
• In addition, cyclosporin A not only inhibits nuclear import of HIV-1 DNA but also inhibits expression of c-Myc protein [11].
• Here we demonstrate that, unlike phosphorylation, p53 invariably undergoes acetylation in cells exposed to a variety of stress-inducing agents including hypoxia, anti-metabolites, nuclear export inhibitor and actinomycin D treatment [12].
• Deletion or alanine substitution of an N-terminal leucine repeat motif present in both RGS4 and RGS16, a domain identified as a nuclear export sequence in HIV Rev and other proteins, promoted nuclear localization of these proteins in COS-7 cells [13].
• We replaced Ser120 by aspartic acid or alanine using site-directed mutagenesis and assessed the effects on nuclear transport kinetics both in vivo (microinjected cells) and in vitro (mechanically perforated cells) in HTC rat hepatoma cells [14].

Biological context of Active Transport, Cell Nucleus

• We show that TK mRNA nuclear transport in this cell can be dramatically altered by introduction of specific DNA sequences into the nucleus [15].
• Nuclear localization of Translin is limited to lymphoid cell lines, raising the intriguing possibility that nuclear transport of Translin is regulated in a physiologically significant way such that active nuclear transport is associated with the lymphoid specific process known as Ig/TCR gene rearrangement [16].
• Furthermore, the nuclear import of Exd correlates with the transcription of an exd-dependent reporter gene in the endoderm [17].
• The Toll signalling pathway, which controls dorsal-ventral patterning during Drosophila embryogenesis, regulates the nuclear import of Dorsal in the immune response, but here we show that the Toll pathway is not required for nuclear import of Dif [18].
• Calcineurin suppresses this futile cycling by a non-catalytic mechanism involving the masking of nuclear export signals on NF-AT targeted by Crm1 [19].

Anatomical context of Active Transport, Cell Nucleus

• These results indicate that CRM1 is an essential mediator of the NES-dependent nuclear export of proteins in eukaryotic cells [20].
• We propose that the docking of RCC1 to H2A/H2B establishes the polarity of the Ran-GTP gradient that drives nuclear envelope assembly, nuclear transport, and other nuclear events [21].
• A leucine-rich nuclear export signal (NES) allows rapid export of proteins from cell nuclei [22].
• Expression of dn-HRH1 in mammalian cells leads to inhibition of splicing and to extensive nuclear export of unspliced pre-mRNA, probably because of the incapability of recycling spliceosome components that normally retain the pre-mRNA in the nucleus [23].
• Inhibition of CD83 cell surface expression during dendritic cell maturation by interference with nuclear export of CD83 mRNA [24].

Associations of Active Transport, Cell Nucleus with chemical compounds

• Conversely, leptomycin B, a cytotoxin that is shown to bind to CRM1 protein, specifically inhibits the nuclear export of Rev and U snRNAs [25].
• Sequence analysis revealed that the cT mutation results in the replacement of a positively charged lysine in wild-type T antigen with a neutral asparagine at amino acid number 128, demonstrating that the alteration of a single amino acid is sufficient to abolish nuclear transport [26].
• Our results indicate that the NLS-binding proteins are NEM-sensitive receptors for nuclear import [27].
• Although MA lacks the canonical leucine-rich nuclear export signal, nuclear export is mediated through the conserved Crm1p pathway and functions in both mammalian cells and yeast [28].
• Here we show that LMB is a potent and specific inhibitor of the NES-dependent nuclear export of proteins [20].

Gene context of Active Transport, Cell Nucleus

• Unlike MDM2, however, MDM4 does not cause nuclear export or degradation of p53 (refs. 9,10) [29].
• The predicted NUP98-HOXA9 fusion protein may promote leukaemogenesis through inhibition of HOXA9-mediated terminal differentiation and/or aberrant nucleocytoplasmic transport [30].
• Both depend on regulatory factors containing rel domains (dorsal and NF-kappa B) that are controlled at the level of nuclear transport [31].
• Nup145p, Nup116p, and Nup100p thus represent a novel class of nucleoporins involved in nucleocytoplasmic transport [32].
• Evidence that Armadillo transduces wingless by mediating nuclear export or cytosolic activation of Pangolin [33].

Analytical, diagnostic and therapeutic context of Active Transport, Cell Nucleus

• A human Rev-interacting protein (hRIP) was originally identified based on its ability to interact with the Rev nuclear export signal (NES) in yeast two-hybrid assays [34].
• Microinjection of anti-NS2 antibodies into infected cells inhibited nuclear export of viral ribonucleoproteins, suggesting that the Rev-like NS2 mediates this process [35].
• We used affinity chromatography on immobilized RanGTP to isolate further candidate nuclear transport receptors and thereby identified exportin 4 as the most distant member of the importin beta family so far [36].
• Site-directed mutagenesis of a putative nuclear targeting signal, identified in the primary structure of deoxycytidine kinase, completely abolished nuclear import of the protein [37].
• After treatment with leptomycin B, a specific inhibitor of CRM1-mediated nuclear export, the accumulation of epitope-tagged FANCA in the nucleus increased, whereas FANCC was affected to a lesser extent and FANCG showed no response [38].

References