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Characteristics, Events, and Stages in Tumorigenesis
Published in Franklyn De Silva, Jane Alcorn, The Elusive Road Towards Effective Cancer Prevention and Treatment, 2023
Franklyn De Silva, Jane Alcorn
The selective packing of molecular cargo in EV-associated mechanisms remains poorly understood [768]. Exosomes (different from the exosome complex involved in RNA degradation [828, 894]), the smallest of the vesicles, are currently a hotspot in the field of cancer and are released by the fusion of multivesicular bodies [838, 839]. Exosomes were first discovered in the 1980s by Johnstone and colleagues and are nanoscale cystic vesicles actively secreted by many kinds of cells to function in the transmission of cell-to-cell information [846, 849, 851, 895]. They are capable of transporting proteins, peptides, metabolites, lipids, nucleic acids, and other components like CD80, MHC-I, and MHC-II that play a major part in intercellular communication including regulation of angiogenesis, fibrosis, and immune response [840, 881, 895].
RNA binding proteins in the control of autoimmune diseases
Published in Immunological Medicine, 2019
Masanori Yoshinaga, Osamu Takeuchi
One type of mRNA decay is induced in a deadenylation-dependent manner. Deadenylation, or poly(A) tail shortening, is mediated by poly(A)-nuclease 2 (PAN2)-PAN3 and carbon catabolite repression 4-negative on TATA-less (CCR4-NOT) deadenylation complexes. This removal of poly(A) tail allows the exosome complex to undergo further 3′–5′ exonucleolytic degradation. Also, deadenylation is followed by decapping via the decapping complex formed by DCP1 and DCP2, which removes the m7G cap. It is also possible that decapping takes place independently of deadenylation [17]. The unprotected 5′ end of mRNAs is then targeted by 5′–3′ exonuclease XRN1.
The role of exosome in autoimmune connective tissue disease
Published in Annals of Medicine, 2019
Tian Zhu, Yiman Wang, Hongzhong Jin, Li Li
DM patients with exceptional antinuclear antibody titres and PM/Scl specificity have been reported; these are rare serological cases with an acute monophasic course. However, the evidence does suggest that autoantibodies can be used as serological markers for accurate diagnoses of myositis-associated conditions and as a monitor of disease behaviour [30]. To date, little is known about the involvement of exosomes in DM and related diseases. However, as the exosome complex is targeted by autoantibodies, we can speculate that exosomes are involved in regulating immune responses.
Encounters with adenovirus
Published in Upsala Journal of Medical Sciences, 2019
Dramatic changes are seen at 24 hpi when infected cells are driven into the S phase. More than 2000 additional genes are now up- and down-regulated (Figure 3). Although most of them are similar in function to those up-regulated at 12 hpi, the number of genes involved in DNA metabolism and DNA replication increases nearly 10-fold. Genes in clusters 13, 14, and 15 include several DNA polymerases, replication factors, histones, and many cell cycle regulators. In addition, genes participating in RNA processing become up-regulated, like genes required for efficient export of polyadenylated RNA and genes encoding components of the exosome complex involved in the degradation and processing of a wide variety of RNA species. Based on their expression level at 36 hpi, the up-regulated genes at 24 hpi fall into four clusters, 13, 14, 15, and 16. Although many functions are shared between them, some differences exist. For the genes in cluster 13, the most significant function is protein translation, RNA processing, and cell cycle, whereas the most significant functions of the others are DNA metabolism and replication, cell cycle, and stress response. The E2F binding sites are common in clusters 13 and 14, as are the binding sites for GABP, NRF1, and ATF/CREB. GABP regulates genes that are involved in cell cycle control, protein synthesis, and cellular metabolism. NRF1 activates the expression of some key metabolic genes regulating cellular growth. The most significant TF binding sites for genes in cluster 15 differed in that the ATF/CREB binding motif becomes more abundant. The ATF/CREB family has diverse functions, controlling cell proliferation and apoptosis. The number of suppressed genes at 24 hpi also increases. They are involved in either cell motion and structure or growth mediated by growth factors. Gene functions involved in cytoskeleton organization are significant in cluster 17, whereas genes implicated in cell adhesion are present in cluster 18.