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Acute and Chronic Transforming Retroviruses
Published in Pimentel Enrique, Oncogenes, 2020
The oncogene v-rel is contained in reticuloendotheliosis virus strain T isolated from turkey. Many differences are observed in the predicted translational products of v-rel and its normal cellular counterpart c-rel, which may account for their differences in transformation potential.80 A similar situation occurs with the transforming protein products of many other acute oncogenic retroviruses, which suggests that, at least for some oncogenes, overexpres-sion of a normal c-onc product is not sufficient by itself to induce oncogenic transformation and that qualitative differences existing between v-onc and c-onc genes are important for determining their oncogenic capabilities. On the other hand, the normal cellular fos gene product is capable of inducing transformation under certain experimental conditions.63 It is thus apparent that neither the presence of viral gene sequences in form of hybrid proteins nor the presence of mutational changes in form of amino acid substitutions are indispensable requisites for the transformation ability of certain oncogene products under specific conditions.
Physiology and Growth
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
One of the last topics exploiting the stringent or relaxed status of the host's rel locus in connection with the RNA phage infection was devoted to polyamine synthesis (Fukuma and Cohen 1973). The presented data indicated a close correlation between the synthesis of RNA and spermidine, suggesting a significant role for this polyamine in the multiplication of the phage R17. Furthermore, the phage R17 and its RNA were found to contain significant amounts of spermidine, but not of putrescine. When isolated at 0.01 M KCl, up to 1000 molecules of spermidine were associated with the R17 virion. The phage R17 RNA isolated with phenol plus sodium lauryl sulfate contained approximately 70–90 molecules of spermidine (Fukuma and Cohen 1975a). Finally, Fukuma and Cohen (1975b) acknowledged the fact that the R17 infection permitted the synthesis of RNA and spermidine in a stringent E. coli strain in the absence of the exogenous essential amino acid, namely arginine in this case. Therefore, the fact of the phage infection as such was suspected to alter the availability of the rel gene product. This conclusion was close to that mentioned above: although phage RNA synthesis may be controlled by the rel locus, this control was different from the host's control over rRNA synthesis (Watson and Yamazaki 1972). In conclusion, the connection of the rel locus status with the inhibition of the phage RNA synthesis generally retained its mysterious character.
Nutraceutical’s Role in Proliferation and Prevention of Gynecological Cancers
Published in Sheeba Varghese Gupta, Yashwant V. Pathak, Advances in Nutraceutical Applications in Cancer, 2019
Aaishwarya B. Deshmukh, Jayvadan K. Patel, Bharat Mishra
NF-κB as a nuclear factor was found to bind to the enhancer element of the immunoglobulin kappa light chain of activated B cells (hence abbreviated NF-κB) [41]. The five members of NF-κB group of proteins identified are RelB, p65 (RelA), NF-κB1 (p105/p50), NF-κB2 (p100/p52), and c-Rel [42–45]. The expression of genes involved in the various processes of transformation and development of tumor cells is regulated by the transcription factor NF-κB by various proinflammatory stimuli such as TNF-α, lipopolysaccharide, IL-1b, and oxidative stress, which induce expression of multiple genes encoding proinflammatory cytokines, growth and angiogenic factors, chemokines adhesion molecules, such as ICAM-1 and e-selectin VCAM-1, and inducible enzymes like iNOS and COX-2 [46]. The apprehension that the c-rel, which is a cellular homologue of the oncogene v-rel, encodes for a NF-κB subunit and binds to the same DNA binding domain has given the first proof of link between NF-κB and cancer [47]. In addition, the detection of active NF-κB in cancer tissues of the patients, including those with lymphoma and leukemia and cancers of breast, prostate, pancreas, oral cavity, colon, liver, and ovary support the link between NF-κB and cancer [48]. All these point to the relevance or importance of NF-κB pathway in cancer, and so this pathway has been manifested as a favored target for therapeutic development.
Effect of inflammation on cytochrome P450-mediated arachidonic acid metabolism and the consequences on cardiac hypertrophy
Published in Drug Metabolism Reviews, 2023
Mohammed A. W. ElKhatib, Fadumo Ahmed Isse, Ayman O. S. El-Kadi
Inactive NF-κB resides in the cytoplasm of every cell as a heterogenous group of hetero- or homodimeric transcription factors comprising different subunits (Aggarwal 2004). These subunits belong to the reticuloendotheliosis (Rel) protein family. The whole five Rel proteins possess the Rel homology domain (RHD) comprising nearly three hundred amino acids which is involved in DNA binding, dimerization, and interacting with NF-κB inhibitor (IκB). These five proteins are NF-κB1 (comprising p50 with its precursor p105), NF-κB2 (comprising p52 with its precursor p100), Rel A (p65), Rel B, and c-Rel. Commonly, the first two proteins are generated as large precursors (p100 and p105) which are further transformed into smaller proteins with transcriptional activity, while the latter three are produced as active transcriptional factors (May and Ghosh 1998; McKay and Cidlowski 1999; Bottex-Gauthier et al. 2002; Aggarwal 2004; Sethi et al. 2008; Prasad et al. 2010).
The effect of N-acetyl cysteine and doxycycline on TNF-α-Rel-a inflammatory pathway and downstream angiogenesis factors in the cornea of rats injured by 2-chloroethyl-ethyl sulfide
Published in Immunopharmacology and Immunotoxicology, 2021
Melad Sabzevare, Farshad Yazdani, Ali Karami, Mohaddese Haddadi, Hossein Aghamollaei, Alireza Shahriary
ROS accumulation to some extent can be a result of the CEES agents that recruit and activate neutrophils and macrophages to induce inflammatory cytokines and signaling pathways. We explored the effects of NAC and Dox on tnf-α and rel-a gene expression, as the main inflammatory pathway. The expression level of TNF-α increased in the cornea of the CEES group, which represented the high level of oxidative stress, rather than healthy rats. Our data showed that NAC could decrease the TNF-α mRNA expression, probably through the cellular redox regulation. This alteration was also illustrated in the reduction of rel-a gene expression following NAC treatment in the long term. TNF-α is one of the pro-inflammatories elevated in the cornea of BALB/c male mice with alkali corneal burns. The injection of infliximab, an anti-TNF-α antibody, was able to reduce inflammatory cytokines such as IL-1β and IL-6 [28]. TNF-α cytokine potentially recruits neutrophil and macrophage (MQ) cells into the injured cornea via inducing the Rel-a to form nuclear factor kappa B (NF-κB) transcription factor [29,30]. Correlation analysis indicated the suppression effect of NAC on inflammatory signals between TNF-α and Rel-a.
RelB regulates basal and proinflammatory induction of conjunctival CCL2
Published in Ocular Immunology and Inflammation, 2021
Li-Fong Seet, Li Zhen Toh, Stephanie W. L Chu, Tina T. Wong
In mammalian cells, the NF-κB family comprises of five different members, namely RelA, RelB, c-Rel, NF-κB1 (p50 and its precursor p105), and NF-κB2 (p52 and its precursor p100). While p105 and p100 are inhibitory proteins, their respective mature forms, p50 and p52, function as active transcription factors. On the other hand, RelA, RelB and c-Rel subunits contain C-terminal transactivation domains that are capable of directly mediating interactions with basal transcription factors and cofactors. The different members can form a variety of homodimers and heterodimers with distinct activities, depending on their participation in either the classical (also known as canonical) or alternative (also known as noncanonical) signaling pathways.5,6 The classical NF-κB cascade is activated by proinflammatory agents such as cytokines and involves the activation of RelA-p50 heterodimers. The alternative pathway, originally associated with immune cell differentiation, maturation and survival and osteoclastogenesis, is activated via a subset of receptors from the TNF family and triggers the production of active RelB-p52 heterodimers.7 Since these two pathways are associated with regulation of potentially opposite inflammatory outcomes,8,9 delineating the contributions of individual NF-κB members is important for understanding the inflammatory response associated with a specific biological, physiological or disease context.1