Mechanism of Transfection
Danilo D. Lasic in 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.
Manipulating the Intracellular Trafficking of Nucleic Acids
Kenneth L. Brigham in Gene Therapy for Diseases of the Lung, 2020
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.
Order Blubervirales: Core Protein
Paul Pumpens, Peter Pushko, Philippe Le Mercier in Virus-Like Particles, 2022
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).
POM121 overexpression is related to a poor prognosis in colorectal cancer
Published in Expert Review of Molecular Diagnostics, 2020
Tengqi Wang, Haibin Sun, Yinshengboer Bao, Riletu En, Yongjing Tian, Wei Zhao, Lizhou Jia
Nucleoporins (Nups) are the chief components of nuclear pore complexes (NPCs) which can regulate cellular signaling between cytoplasm and nucleus [18]. Except transport-independent functions, Nups also participate in cancer formation and progression. Tpr is the first validiert Nup contributing to the mechanism of oncogenesis, and decreased in human colorectal tumors [19]. Nup98 expression decreased in murine and human hepatocellular carcinomas and acts as a potential tumor suppressor through regulatingp53 target genes [20]. Nup88 overexpressed in a large number of tumors, such as CRC, endometrial cancer, breast cancer [21–23]. Nup62 is highly expressed in elevated in squamous cell carcinomas and controls cell fate through regulation of p63 nuclear transport [24]. In addition, Nup93, Nup188, Nup205, Nup358 and other Nups also play a role in colon cancer cells [25,26]. Different Nups show different expression level in cancers, but no doubt that some of them affect tumorigenesis and progression. POM121 is reported to overexpress in lethal prostate cancer, but little is known its role in CRC.
Steroid-resistant nephrotic syndrome: pharmacogenetics and epigenetic points and views
Published in Expert Review of Clinical Pharmacology, 2020
Seyede Mina Hejazian, Sepideh Zununi Vahed, Hakimeh Moghaddas Sani, Ziba Nariman-Saleh-Fam, Milad Bastami, Seyed Mahdi Hosseiniyan Khatibi, Mohammadreza Ardalan, Nasser Samadi
Nuclear pore complex (NPC) on the nuclear membrane is the assembly of nucleoporins. NPC translocates biomolecules between the nucleus and cytoplasm. Mutations in any of its components can lead to NPC dysfunction. Several mutations in NPC components have been found in SRNS patients [71–73]. A recent study revealed that the mutations in two components of the inner ring of the NPC (NUP93 and NUP205) and exportin5 are detected in early-onset familial SRNS and FSGS patients. Identified NUP93 mutations impair pore formation (deletion of exon 13, p.Arg388Trp and p.Lys442Asnfs*14) or disrupt NUP93-SMAD4 or NUP93-importin7 (K442Nfs*14, G591V and Y629C) interactions [74]. In another study, mutations in four components of the outer ring of the NPC (NUP107, NUP85, NUP133, and NUP160) were observed to be related to familial SRNS. In addition, polymorphisms in the Importin 13 encoding gene resulting in increased GC sensitivity because of the increased availability of glucocorticoids in the nucleus [75]. From these two studies, the SMAD4 signaling pathway and Cdc42 protein are recognized as effectors in the pathogenesis of SRNS [73].
TMEM48 promotes cell proliferation and invasion in cervical cancer via activation of the Wnt/β-catenin pathway
Published in Journal of Receptors and Signal Transduction, 2021
Xiao-Ying Jiang, Li Wang, Zong-Yin Liu, Wen-Xia Song, Mi Zhou, Lan Xi
Nuclear pore complexes (NPCs), embedded in nuclear envelopes to promote molecule exchanges between nucleus and cytoplasm, consist of multiple copies of almost 30 different nucleoporins [12]. NPCs not only take part in nucleocytoplasmic transport but also play an essential role in the regulation of genome stability, DNA replication, cell death and other crucial cellular processes [13–15]. Notably, nucleoporin changes have been reported to exert a critical effect on the progression of various cancers [16–18]. With 6 membrane-spanning segments, transmembrane protein 48 (TMEM48) is the most conserved membrane nucleoporin [19]. Mansfeld et al. found an important role of TMEM48 in NPC and nuclear envelope assembly [20]. Moreover, TMEM48 has been demonstrated to be implicated in meiosis and gametogenesis [21]. Recently, TMEM48 has been reported to be closely related to the development of lung cancer [22]. However, little is known about the specific role of TMEM48 in CC.
Related Knowledge Centers
- Cytoplasm
- Eukaryote
- Macromolecule
- Nuclear Envelope
- Nuclear Lamina
- Nuclear Pore
- Cell Nucleus
- Phenylalanine
- Nuclear Pore Glycoprotein P62
- Copii