The C1ORF112 gene initially drew attention when it was found to be strongly co‐expressed with several genes previously associated with cancer and implicated in DNA repair and cell cycle regulation, such as RAD51 and the BRCA genes. The molecular functions of C1ORF112 remain poorly understood, yet several studies have uncovered clues as to its potential functions. Here, we review the current knowledge on C1ORF112 biology, its evolutionary history, possible functions, and its potential relevance to cancer. C1ORF112 is conserved throughout eukaryotes, from plants to humans, and is very highly conserved in primates. Protein models suggest that C1ORF112 is an alpha-helical protein. Interestingly, homozygous knockout mice are not viable, suggesting an essential role for C1ORF112 in mammalian development. Gene expression data show that, among human tissues, C1ORF112 is highly expressed in the testes and overexpressed in various cancers when compared to healthy tissues. C1ORF112 has also been shown to have altered levels of expression in some tumours with mutant TP53. Recent screens associate C1ORF112 with DNA replication and reveal possible links to DNA damage repair pathways, including the Fanconi anaemia pathway and homologous recombination. These insights provide important avenues for future research in our efforts to understand the functions and potential disease relevance of C1ORF112.
Susceptibility of gastrointestinal dysmotility increases with age-associated colonic degeneration. A paucity of remedies reversing colonic degeneration per se hinders the fundamental relief of symptoms. Here we discovered the correlation between colon degeneration and altered nicotinamide adenine dinucleotide (NAD) level in aged mice. Compared to 3-month-old young controls, 2-year-old mice showed a spectrum of degenerative colonic phenotypes and exhibited a significant elongated transit time and slowed stool frequency in the context of Lomotil-induced slow-transit constipation. Despite upregulated colonic tryptophan hydroxylases expression, serotonin release and expression of colon-predominant type IV serotonin receptor, reduced viability of interstitial cells of Cajal while enhanced aquaporins (Aqp1, 3 and 11) led to a less colonic motility and increased luminal dehydration in aged mice. Notably, this colonic degeneration was accompanied with reduced key NAD+-generating enzyme expression and lowered NAD+/NADH ratio in aged colon. Three-month continuous administration of beta nicotinamide mononucleotide, a NAD+ precursor, elevated colonic NAD+ level and improved defecation in aged mice. In contrast, pharmacological inhibition of nicotinamide phosphoribosyltransferase, the rate-limiting enzyme for NAD+ biosynthesis, induced a reduction in colonic NAD content and impaired gastrointestinal function in young mice. Taken together, these findings suggest the beneficial effect of NAD+ in maintaining colonic homoeostasis and reactivating NAD+ biosynthesis may represent a promising strategy to counteract age-related gastrointestinal degeneration.
Plants in nature may face a wide range of favorable or unfavorable biotic and abiotic factors during their life cycle. Any of these factors may cause stress in plants; therefore, they have to be more adaptable to stressful environments and must acquire greater response to different stresses. The objective of this study is to retrieve and arrange data from the literature in a standardized electronic format for the development of information resources on potential stress responsive genes in Arabidopsis thaliana. This provides a powerful mean for manipulation, comparison, search, and retrieval of records describing the nature of various stress responsive genes in Arabidopsis thaliana. The database is based exclusively on published stress tolerance genes associated with plants.
Three pharmacogenetic differences (the acetylation, debrisoquine 4-hydroxylase, and Ah locus polymorphisms) appear to be associated with increased risk of environmentally caused human cancer. The latter two polymorphisms represent differences in P450 gene expression. It is predicted that molecular biological studies will soon provide a means (RFLP patterns or expression vector assays) of predicting individual cancer risk related to these polymorphisms. At the present time, only the Ah locus polymorphism has been explored at the molecular biological level. More than 30 P450 genes, including eight from the human, have been isolated and sequenced to date. The P450 gene superfamily comprises at least eight families, including one gene family that has diverged more recently into at least five subfamilies. The P450 gene superfamily can be regarded as ancient, with Pseudomonas and human amino acid sequences displaying a small but significant resemblance in the region of the enzyme active-site. P450 enzymic activity can be depressed 30-60% by immunosuppressive agents. The mechanism of this effect is unknown. This phenomenon can become clinically important if a cancer patient who is taking any chemotherapeutic drug that is detoxified by P450 then receives one of these agents. The Ah receptor-controlled gene expression, positive and negative control elements, and negative autoregulatory loop--best characterized in the mouse P(1)450 gene and upstream sequences, plus the receptor-defective and the P(1)450 enzymic activity-negative mutants in mouse cell cultures--provide the molecular geneticist with an exciting model system for studying the regulation of a clinically relevant gene family. The high degree of homology in a 220-bp segment between mouse and human P(1)450 sequences (about 1140 to 920 bases upstream from the mRNA cap site) suggests that this positive regulatory element (dioxin-inducible enhancer which also controls constitutive gene expression) is conserved between Mus domesticus and Homo sapiens.
The mammalian sirtuin family consists of seven proteins, three of which (SIRT3, SIRT4, and SIRT5) localise specifically within mitochondria and preserve mitochondrial function and homeostasis. Mitochondrial sirtuins are involved in diverse functions such as deacetylation, ADPribosylation, demalonylation and desuccinylation, thus affecting various aspect of cell fate.
We predicted the structure of TMPRSS2 (transmembrane protease serine 2), a host protein that truncates spike protein of SARS-CoV-2. Then we docked 18 anti-viral compounds found in Indian spices against the catalytic domain of TMPRSS2. We then performed rigorous molecular simulation dynamics simulation to screen the best natural phytochemical which could act as a potential inhibitor of TMPRSS2 activation. <br>
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