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Order Blubervirales: Core Protein
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
The most important targets of the HBc protein during HBV replication were the nuclei of infected cells, as the HBc protein shuttled between the nucleus and cytoplasm. The importin alpha and beta complexes, or importin alpha alone, were regarded therefore as potential transporters of capsids to the nuclear pores (Kann et al. 2007), where capsids interacted with nucleoporin 153 and dissociated during nuclear entry (Rabe et al. 2009; Schmitz et al. 2010).
Manipulating the Intracellular Trafficking of Nucleic Acids
Published in Kenneth L. Brigham, Gene Therapy for Diseases of the Lung, 2020
Kathleen E. B Meyer, Lisa S. Uyechi, Francis C. Szoka
One of the first isolated nucleoporins, p62 isolated from rat liver, displays the XFXFG motif. This protein tightly complexes with two other nucleoporins, p58 and p54 (107), and has been localized throughout the pore complex but mainly to the internal core of the NPC. Depletion of p62 and associated proteins from the nuclear envelope results in the loss of protein import function (107), and the direct interaction between mRNA and p62 implicates the nucleoprotein also functions in mRNA export (108). p62 also appears to play a structural role in the NPC, since the nucleoprotein is necessary for the in vitro formation of NPCs in annulate lamellae (94). Therefore p62 is involved with both import and export functions as well as providing structural support.
Mechanism of Transfection
Published in Danilo D. Lasic, LIPOSOMES in GENE DELIVERY, 2019
We shall follow a genosome with given physicochemical characteristics which determine its biological properties during the transfection process. Its stability and interaction characteristics dictate its fate in biological systems, and we shall look at interactions with cells, genosome/DNA entry into the cytoplasm, and interactions in the cytoplasm leading to the entry into the nucleus. Because we can, at present, control mostly behavior up to the DNA release in the cell cytoplasm, we shall concentrate on the first part of the transfection, i.e., transfer of plasmid from the outside of the cell into the cytoplasm. The second part of transfection, consisting of the transfer of the plasmid from cytoplasm into the nucleus, is still very obscure. It is possible that it can be better controlled by special DNA inserts than by delivery vehicles. While there is a constant efflux of nucleic acids from the cell nucleus, there are in nature only viral and spermal DNA which efficiently travel in the opposite direction. There are, however, many proteins which shuttle through the nuclear membrane, including transporters, nucleoporins, and others, which may contain nuclear localization sequences. These are regions rich in basic amino acids and can bind nucleic acids. Such complexes enter nuclei through a nuclear pore complex, a protein which regulates a pore with diameter of approximately 100 nm.
Exploiting active nuclear import for efficient delivery of Auger electron emitters into the cell nucleus
Published in International Journal of Radiation Biology, 2023
Andrey A. Rosenkranz, Tatiana A. Slastnikova, Mikhail O. Durymanov, Georgii P. Georgiev, Alexander S. Sobolev
For most of the cellular life, the contents of the cell nucleus are separated from the cytoplasm by the nuclear envelope, which consists of two phospholipidic membranes and intermembrane space that are permeated by numerous NPC (Lin and Hoelz 2019). NPCs are supramolecular protein structures that form rounded holes in the nuclear envelope where both nuclear membranes are fused. NPCs are embedded within these holes and form a stable protein scaffold. On the nuclear side, the scaffold forms eight extended fibers that are connected in a distal ring and form the nuclear basket. Another eight flexible fibers extend into the cytoplasm. Additional fiber-like extensions in a central opening generate the permeability barrier, which controls the import and export of macromolecules (Knockenhauer and Schwartz 2016). The main components of the eukaryotic NPC, called nucleoporins, are a family of approximately 30 proteins that form a part of the scaffolding and transport functions of NPC. The outer diameter, inner diameter of the central transport channel, height, and molecular mass of the human NPC is approximately 120 nm, 42.5 nm, 80 nm, and 110 MDa, respectively (Lin and Hoelz 2019).
Bioinformatics analysis of the expression and clinical significance of the NUP210 Gene in acute myeloid leukaemia
Published in Hematology, 2022
Nuclear pore complexes (NPCs) are large multiprotein structures, which act as gatekeepers regulating the flow of macromolecules through the nuclear envelope. Nucleoporins (Nups) are the basic structural and functional units of NPCs, which, in addition to nucleocytoplasmic transport, regulate other cellular functions such as gene expression, DNA damage repair, mitosis, and differentiation in a transport-independent manner [1,2]. Accumulating evidence indicates that Nups play an important role in the occurrence and development of numerous types of cancer. Thus, high expression of NUP88 is associated with tumour invasion in breast cancer, colorectal cancer, and melanoma [3–5], whereas NUP62 may promote the progression of ovarian, prostate, and squamous cell carcinomas [6–8]. Furthermore, rearrangements of NUP98 and NUP214 genes have been reported to be associated with various types of haematological malignancies [9].
TAR DNA-binding protein of 43 kDa (TDP-43) and amyotrophic lateral sclerosis (ALS): a promising therapeutic target
Published in Expert Opinion on Therapeutic Targets, 2022
Yara Al Ojaimi, Audrey Dangoumau, Hugo Alarcan, Rudolf Hergesheimer, Patrick Vourc’h, Philippe Corcia, Débora Lanznaster, Hélène Blasco
For instance, TDP-43 plays an important role in the nucleus through the regulation of transcription and the response to DNA damage, which are dysregulated in ALS [16]. The mislocalization of TDP-43 into the cytoplasm was associated with abnormal shuttling between the nucleus and the cytoplasm. In fact, abnormal nucleocytoplasmic transport has been reported in several age-related neurodegenerative diseases including ALS with TDP-43 pathology [24]. Fibroblasts, iPSC-derived neurons and brain tissues from ALS patients with TDP-43 pathology showed morphologically defective nuclear membranes and nuclear pore complexes [25]. It is still not well understood if TDP-43 aggregates lead to nucleocytoplasmic transport defects or vice versa. On one hand, cytoplasmic TDP-43 aggregates were shown to sequester specific nucleoporins and transport factors, thus altering the normal nuclear import of proteins and export of RNA, exacerbating the depletion of TDP-43 from the nucleus and causing cell death [25]. On the other hand, defective nucleocytoplasmic transport was found to trigger TDP-43 proteinopathy and cytoplasmic aggregation [26]. Exclusion of TDP-43 from the nucleus will have global effects on mRNA alternative splicing, including transcripts that are crucial for the survival of neurons.