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- Table of Contents
Facts about Alpha-ketoglutarate-dependent dioxygenase FTO.
Especially demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes. Has no activity towards 1- methylguanine.
Mouse | |
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Gene Name: | Fto |
Uniprot: | Q8BGW1 |
Entrez: | 26383 |
Belongs to: |
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fto family |
Alpha-ketoglutarate-dependent dioxygenase FTO; EC 1.14.11.-; fat mass and obesity associated; Fat mass and obesity-associated protein; FTO; KIAA1752protein fto; MGC5149
Mass (kDA):
58.007 kDA
Mouse | |
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Location: | 8 C4-C5|8 44.34 cM |
Sequence: | 8; |
Ubiquitous. Detected in brain, brain cortex, hypothalamus, cerebellum, liver, pancreas, heart, kidney, white adipose tissue and skeletal muscle. Most abundant in the brain, particularly in hypothalamic nuclei governing energy balance.
The FTO marker targets mTOR which is a crucial regulator of obesity and cancer. It can directly affect this pathway or indirectly block it. This article will explain how FTO can be employed to treat obesity and cancer. Although it is not known whether FTO can be effective in the development of tumors in melanoma, research is ongoing. It is also able to block the production of anti-PD-1 antibodies.
The FTO marker is a non-heme oxidase of iron that has been linked to obesity. The FTO gene sequence is found in a variety of marine algae and vertebrates, although it isn't included in public databases. It shares features with Fe (II) and 2-oxoglutarate oxygenases. The FTO marker is used to identify metabolic pathways and genes as well as those that are associated with obesity.
Despite the strong correlation between FTO SNPs and BMI These findings are highly informative. While these associations are intriguing however, they pose issues for further mapping. Fine-mapping efforts focused on the identification of SNPs within the relevant genomic region. Furthermore, a larger percentage of individuals may not have the exact genetic code of a gene in their genome, making further research difficult.
It is possible that m6A methylation is responsible for the increased expression of FTO in fat mice. FTO knockdown and overexpression alters the levels of proteins in m6Am-methylated targets. These findings indicate that FTO could play a crucial role in the dynamic translation regulation of obesity. This discovery is an exciting breakthrough in research. These findings represent a major breakthrough in research. More studies are needed to discover the way in which the FTO marker functions in metabolic processes.
In conclusion, studies in mice suggest that the FTO marker is a major contributor to the development of obesity. The FTO gene is also linked to the development of metabolic diseases, including Type 2 diabetes and hypertension. The clinical implications of the FTO marker are significant. It can aid in early detection of obesity and it could also be used to treat and prevent this condition. There are a variety of potential uses for the FTO gene.
The anti-leukemic effects of FB23-2 were confirmed using m6A-seq. The FB23-2 inhibitor inhibited cell proliferation and reduced colony-forming unit capacities in MONOMAC6 cells. It also induced cell death. Through FTO-dependent mechanisms, the drug blocks leukemogenesis in AML cells.
FB23-2 has the capability of inhibiting FTO-mediated demethylation. The inhibitor's IC50 is 140 times more than MA. It is also more potent than MA at preventing FTO-mediated methylation. The inhibition of FTO is caused by an uncoupling protein that originates from FB23-2. This results in improved leukemogenesis inhibition.
In mice, treatment with FB23-2 delayed the development of leukemogenesis in vivo. Twenty milligrams/kg FB23-2 was given daily to female BALB/c mice, and weight was measured on day 15. FB23 levels were measured using LC-MS/MS/MS/MS/MS/MS/MS/MS/ of mice with MONOMAC6 xenotransplantation have been analyzed using Kaplan-Meier survival curves.
The inhibition of m6A-methylation by FB23-2 has been demonstrated in xenografts and human AML cell lines. A m6A-dependent process further confirmed the anti-leukemic properties of FB23-2. The inhibitor inhibits the expression of LILRB4 mRNA which is essential for leukemogenesis. FB23-2 reduces the growth of MONOMAC6 and NB4 cells.
In the study of secondary transplantation there were a variety of human AML cells were transplanted into PDX mice. The secondary recipients mice showed more engraftment after treatment with DMSO or FB23-2. The number of functional LSCs was reduced in secondary recipients mice due to DMSO and FB23-2 treatments. The secondary recipients of human AML cells had a higher prognosis as compared to controls.
Inhibitory assays of FB23-2 were carried out using AlphaLISA technology. Different concentrations of FB23-2 were pre-incubated with human recombinant caspase 2 for 15 minutes at temperatures of room temperature. After incubation the inhibitors were mixed with a mixture of (NH4)2Fe(SO4)2 and L-ascorbic acid. Then the biotinylated H4-derived peptide (BRD4) and an anti-GST donor antibody were added to each well.
The current study demonstrated that boster bio FB23-2 is able to inhibit the development of tumors from melanoma in a dose-dependent fashion. The formulated compound was administered intraperitoneally to SD rats. Blood samples were taken via retro-orbital bleeding into EDTA-containing tubes. Plasma samples were collected, and their concentrations were determined by LC-MS/MS. All analyses were carried out using the Phoenix 1.4 software. The area under the curve of concentration was calculated.
The FB23-2 compound blocks the expression of PD-1 and CD73 in BM cells and enhances the infiltration of CD8+ T cells, thereby abating anti-PD-L1 resistance. The compound also increases the levels RARA and ASB2 within NB4 cells and MONOMAC6 cell cells. However, these findings are not independently verified. However, these promising findings suggest that FB23-2 could be a viable treatment option to PD-L1-resistant tumours.
Although PD-L1-targeted therapy for immune disorders has demonstrated remarkable efficacy in the treatment of solid tumoursbut a significant number of patients have acquired immunity. Understanding the causes of resistance is essential to improve the effectiveness of anti-PDL1 treatments. This compound blocks the activity of the demethylase m6A, which is responsible for PD-1 resistance.
Some patients might develop a primary resistance to anti-PDL1 treatment. The host immune system could also play an active role in this process. Immunoediting cancer cells can alter the immune system's context which can result in tumor-specific T cell overexpression and ineffectiveness. Therefore the immune cells are unable to create memory T cells and the therapeutic response is not able to last.
The blockade of PD1/PDL1 is also connected with the infiltration of MDSCs throughout the body. The effectiveness and efficacy of immunotherapy against PD-1 could be enhanced by selectively eliminating MDSCs. Furthermore, this type therapy can be synergistic and the combination of anti-PDL1 blockade and CD40 inhibition has been shown to have superior survival outcomes.
Furthermore, tumors that have significant mutational burdens are more likely to create Neoantigens. They can trigger antigen-specific T cell reactivity. They also have high levels of mutations which are crucial for antitumor immunity. Moreover, mutational burden is very high in cancers containing mismatch repair genes, and these tumors are tolerant to treatment with anti-PD-1.
Moreover, the B2M locus is linked to an increased number of tumors resistant to anti-PD1/PDL1 therapies. The B2M region also has a high rate of heterozygosity loss both among responders and non-responders. This phenomenon, along with other causes of primary ICB resistance is related to low objective response rates. These findings suggest that anti-PD1 treatments may not be effective in patients suffering from B2M mutations.
PMID: 10501967 by Peters T., et al. Cloning of Fatso (Fto), a novel gene deleted by the Fused toes (Ft) mouse mutation.
PMID: 17991826 by Gerken T., et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase.
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